Биолог Сидни Тэмм: случайные находки и важность непредвзятого взгляда на данные

I was able to work for five weeks of the summer of 2011 at the Marine Biological Laboratory in Woods Hole. This is the one place that all biologists should want to spend time, whatever the focus of their interests and research. Alas, too many don’t. I learned much that summer as MBL lived up to expectations, as did The Captain Kidd. My only regrets are that it took me so long to get there and that I will probably not be able to return. MBL News has an article entitled Chance Favors the Curious: How Serendipity Drives Scientific Discovery (July 31, 2026), about the work of Sidney L. Tamm. Dr. Tamm is a biologist’s biologist, and I have been following his work at a distance since the 1970s. I was honored to meet him at a small scientific meeting in 2016. We had a friendly scientific argument about which organism living today is most similar to the original animal and thus may represent our initial animal ancestor. [1] Our conversation proved to me that our current working biologists would be in a better position to make discoveries if Dr. Tamm and his research were better known. If discovery is the goal, a biologist must always be on the lookout for the unusual because in biology that is where discoveries hide. From Chance Favors the Curious: Tamm’s serendipity began in the 1970s with a termite-infested grapefruit tree. His colleague at Indiana University had removed the tree from his mother’s yard and donated its logs to Tamm, who had been researching protozoa in termite hindguts. Thinking little of it, Tamm let an undergrad examine the single-celled microbes. But then, the student reported something that struck him as odd: a protozoan’s head was rotating continuously in the opposite direction of its body. This, Tamm realized, would only be possible if its cell membrane was fluid. A closer look confirmed Tamm’s suspicion, but the idea of a fluid cell membrane contradicted what almost everyone believed at the time. “People were very skeptical,” said Tamm. No one had ever visualized a fluid membrane before, though it had been proposed earlier on. While it took time to be accepted, Tamm’s discovery (was) so foundational that it ended up in biology textbooks. Dr. Tamm has described his career as a discoverer in Novel Cell Motility of Protozoa Living in the Hindgut of Termites, in the independent online Journal of Trial & Error: A remarkable symbiotic protozoan in the hindgut of termites was accidentally discovered. Its head and body continuously rotated in opposite directions without stopping or reversing directions. Rotations included the plasma membrane of each part of the cell, and the membrane was continuous across the surface shear zone. This protozoan offers direct visual evidence for the fluid nature of cell membranes, and is the first known example of a rotary motor in eukaryotic cells. The rotary motor is an axostyle that runs through the protozoan like a driveshaft and generates relative torque along its length. The entire plasma membrane of the cell is actually fluid and adheres to the underlying cytoplasm/cytoskeleton, passively following its movements. Cell membranes clearly do not determine the shape or movements of cells. Ectosymbiotic rod bacteria attached to the cell surface are flagellated and propel the protozoan, the first known case of prokaryotic flagella driving locomotion of eukaryotic cells. Why does this matter? This first observation of membrane fluidity was made during the second golden age of cell biology when the discipline was emerging from a static cytology, which had defined the first golden age of cell biology. [2] After twenty years of trial and error, the first complete and still the reigning model of biological membranes (with relatively few addenda) was published in Science in 1972 by S.J. Singer [3] and Garth L. Nicholson. I still assign this paper to students. Some go to the trouble of reading The Fluid Mosaic Model of the structure of Cell Membranes (paywall). They will be good scientists and physicians. Perhaps the keyword in this title is “fluid.” Without fluidity cell membranes simply cannot function in cell division, cell motility, and the transmission of signals from the outside of a cell to the inside (as in telling a cell to divide or not in cancer progression). The existence of membrane fluidity was a sticking point when the fluid mosaic model was proposed. Sidney Tamm and his wife Signhild, showed Direct Evidence for Fluid Membranes (1974) at about the same time others were demonstrating this by other methods. The Tamm’s did it because they were open to new evidence when doing basic biological research on seemingly odd organisms that inhabit the gut of termites and allow them to digest wood. Dr. Tamm’s second serendipitous discovery was the first rotary motion in cells and that his was powered by ATP, the proverbial “energy currency of the cell”: Another novel discovery was the nature of the rotary mechanism that turns the head relative to the body of Caduceia — the first example of a rotary motor in higher (eukaryotic) cells. Chance observations and inhibitor experiments indicated that the four flagella (think of the tail of a sperm cell) which arise from the head do not turn it. Instead, the motor is internal and consists of a cytoskeletal rod (axostyle) which runs through the cell like a driveshaft from the head to the posterior end, and uses ATP as the energy source…Surprisingly, the molecular basis of force production by this rotary motor has still not been determined. Another question which has not been followed up is: Why do parts of the cell rotate at all? What is the function of opposing rotations of the head and body? The third serendipitous discovery was the symbiosis between the termite hindgut protozoan Caduceia versatillis and bacteria: I had also noticed that the 2,000 – 3,000 ectosymbiotic rod bacteria attached to the head and body were aligned end-to-end in parallel rows of specialized open pockets of the cell membrane. Surprisingly, the rod bacteria had bacterial flagella on their exposed side, even though they normally never leave the surface of the protozoan host. Flagella of bacteria (called prokaryotes), which do not have a true nucleus, are much simpler than microtubular flagella of eukaryotic cells with nuclei… It then dawned on me that the flagella of the attached rod bacteria must be involved in the vigorous contact-induced gliding locomotion of Caduceia. So I performed extensive experiments to test this idea. … Locomotion of Caduceia is thus powered not by the cell’s own flagella, nor by its rotary axostyle, but by the flagella of thousands of rod bacteria which live on its surface. Since bacterial flagella rotate, an additional novelty of this system is that the surface bearing the prokaryotic rotary motors is turned by the eukaryotic rotary motor within. Why does this matter? That the termite gut is filled with other living organisms has been known for more than 100 years (pdf). But this case is a clear, mechanistic example of the importance of bacterial and protozoan symbiosis within the gut of an animal. Or, to put it in the current vernacular, the microbiome. As we know now, our microbiome has been implicated in all aspects of human health and disease. The research described here anticipated the microbiome as something essential to a healthy life rather than a disease state. Continuing in the larger sense, why does this matter? Because discovery in biology is often the result of, if not accident, serendipity accompanied by the capacity to see new questions in the data and then answer them obliquely if necessary. Theory in biology is not the same as in cosmology, astrophysics, physics, and chemistry. Biology can be studied from the level of molecules to ecosystems but compared to these other disciplines the facts of biology have been contingent upon evolution during three billion years of tinkering since life emerged on planet Earth. For example, my favorite protein has a two-billion-year evolutionary history going back to the divergence of plants from the lineage that includes animals. Therefore, it must be studied as a thing sui generis, albeit in an evolving multicomponent assembly that has grown from three or four proteins in our simple ancestor to more than fifty in humans. Any given sodium atom or Higgs boson is the same as any other. Or as Dr. Tamm puts it: I accidentally found this remarkable protozoan that I certainly was not looking for. A series of fortunate chance encounters and situations, with occasional flashes of sagacity, led to three serendipitous discoveries about protozoa and cells in general: (1) cell membranes are visually fluid and allow unidirectional rotational shear between different regions; (2) the rotary motor in the best studied protozoan is a cytoskeletal driveshaft that generates constant relative torque along its length; and (3) flagella of thousands of ectosymbiotic rod bacteria can propel the host cell. These unexpected discoveries have changed our understanding of how prokaryotic and eukaryotic cells function and can live beneficially together. Moreover, most of his research has been done MBL, which like other similar laboratories, has been the font on much biological knowledge. They are currently in distress, especially with the instrumentalization of biological research that has been steadily encroaching on discovery due to the downstream effects of the Bayh-Dole Act of 1980. This situation has been described recently in Saving science by the sea by Susan Fitzpatrick and Jane Maienschein [4]: As funding for science tightens across the United States, attention has turned to pressures faced by universities and biomedical research institutions. An often overlooked part of the nation’s science ecosystem, however, are the small, independent marine laboratories that are also bearing the brunt of funding cuts and other constraints imposed by the Trump administration. These institutions have long nurtured generations of scientists—from high school students to Nobel laureates—and precipitated discoveries that have advanced modern science. Yet they now face an uncertain future, and losing them would eliminate not only a powerful convergence of research and education but also a wellspring of scientific advancement. Marine laboratories occupy a rare niche. They are mostly independent but often loosely affiliated with universities by sharing faculty, space, or other resources. They host students and scientists from weeks to months, mixing disciplines and experience levels that break down traditional academic silos across the spectrum of life sciences, from molecular to microbial to ecological. The knowledge that many of the participants will be there for only a short period creates a sense of urgency for thinking beyond the typical and asking questions that challenge assumptions and lead to exploring problems in new ways. People come to work intensively in this atmosphere and in nonheirarchical teams, sharing ideas over meals and debating hard questions long into the night. They work together, live together, and share the excitement of discovery together. Just one example of the fecundity of these laboratories suffices, as explained in this interview with Tim Hunt, whose research used sea urchins. Without this, the control of cell division would have remained a black box for a long time: Tim Hunt took an undergraduate degree in Natural Sciences at Cambridge in 1964, and his PhD and subsequent work focussed on the control of protein synthesis until 1982, when his adventitious discovery of the central cell cycle regulator cyclin, while he was teaching at the Marine Biological Laboratory in Woods Hole, redirected him to the study of cell cycle regulation. From 1990 to his retirement Tim worked in the Clare Hall Laboratories of Cancer Research UK. He shared the Nobel Prize in Physiology and Medicine with Lee Hartwell and Paul Nurse in 2001 (who used two evolutionarily divergent yeasts) and talked to us about the series of coincidences that led him to the prizewinning discovery. Although cyclins are now the targets chemotherapeutic agents against cancer, it is safe to say that none of this research would have dovetailed with the “priorities” of the current American administration. As we have discussed before, the opportunity costs of losing these laboratories – where thousands upon thousands of students and scientists have worked together to answer hard questions – are not calculable, but they are large. This research could be generously funded in perpetuity for the cost of one Ford class aircraft carrier. And the research would be effective, which is just one more thing to think about as we consider abandoning, or not, our all-war-all-the-time-everywhere insanity, one way or another. Notes [1] Not to get too far into the weeds, but that creature might be Trichoplax adhaerens, until recently the only representative of phylum Placozoa; three other placozoans are recent discoveries, with possibly more to come. Individual placozoans are motile sheets of several types of cells and often can be found in saltwater aquaria. They have animal-like life cycles. A description of Trichoplax is here. Given the contents of the Trichoplax adhaerens genome, it is a strong candidate for the first animal (research still in progress). [2] The first golden age of cytology/cell biology was defined by E.B. Wilson in his The Cell in Development and Heredity (1896, 1915, 1925). The third edition should be read by all cell biologists, but it isn’t, even when I offer it to them. The original title of the flagship Journal of Cell Biology (Rockefeller University Press) was the Journal of Biophysical and Biochemical Cytology. Cytology was essentially descriptive and used biochemical and biophysical approaches. Cells were ground up and their contents analyzed biochemically or they were examined using a microscope. This led to increasingly mechanistic explanations of cell behavior. Of the original editors of this journal, Albert Lehninger was a biochemist who focused on bioenergetics (and wrote the first and still best textbook of biochemistry), George Palade was awarded a Nobel Prize for his contributions to the structure and function of cells, and Keith R. Porter, a colleague of Palade, used the electron microscope to become “The Father of Cell Biology” despite not being included in the Nobel pantheon. As an aside, the late, great Barbara Ehrenreich received a PhD in cell biology at Rockefeller University before becoming the essential critic of society who first defined the Professional Managerial Class (PMC). [3] S.J. Singer was also an author of the paper from Linus Pauling’s research group that identified sickle cell anemia as the first genetic disease caused by a mutation in hemoglobin that causes the protein to polymerize and form sickle shaped red blood cells: Sickle Cell Anemia: A Molecular Disease. The most remarkable thing about this paper is the completeness with which it described sickle cell disease, in 1949. [4] Jane Maienschein has been a leading historian of biology for the past forty years. Her Defining Biology: Lectures from the 1890s (Harvard University Press, 1986) is the source for understanding the work and the influence of pioneering biologists as experimental biology became a mature scientific discipline. The lectures in the book were given at MBL by E.B. Wilson, Wilhelm Roux, E.G. Conklin, Thomas Hunt Morgan, and Jacques Loeb, among others. Equivalent marine laboratories are in Plymouth, Roscoff, Naples, and Friday Harbor.