Over the Rooftops of Time: Jewish Stories, Essays, Poems

Root Causes: Stem Cells and the Tower of Babel

Root Causes Stem Cells and the Tower of Babel Like Babel, a “lunatic tower launched at the stars,” the dream of finding the hematopoietic stem cell, progenitor of all other blood cells, has haunted researchers for years. To recover the source. As in language, to discover the single primal alphabet that lies behind our present discord, “behind the tumult of warring tongues which followed on the collapse of Nimrod’s ziggurat .”9 To find the elusive primordial cell, rare in the bone marrow, that gives rise to platelet, neutrophil, macrophage, lymphocyte, erythrocyte. As from the mythology of languages, we imagine the hidden contours of the underlying speech of which our words are shards. It is unity we are after: that a single cause might explain all of life; that we are descended from a common ancestor; that our language was once intelligible to all; that a unified field theory would show us a way to marry gravity with electromagnetism ; that the formation of our planet could be traced back to a single knowable moment; that we would find 1 2 1 at the bottom of the ocean a protoplasmic substance out of which complex life developed. At times the evidence has pointed to beautiful underlying structures that organize immense bodies of information. Take the double helix, the molecular structure of the gene. That extraordinary double-hung staircase took Sir Thomas Browne’s unwitting Chain of Being (“There is in this Universe a Stair, rising not disorderly or in confusion, but with a comely method and proportion.”), a thoroughly eighteenth-century construct asserting the immutability of species, and brought it fully to life. Darwin’s theory of evolution established the phylogenetic relationships among all forms of life, turning the key in the lock of Sir Browne’s static proposition. The double helix, where a single chain serves as template for the synthesis of a complementary chain (“A structure this pretty just has to exist,” wrote James Watson, one of its decipherers.), turned the key in that lock a second time. Or take the recently discovered presence of a kind of genetic soup in the great oceans, virus particles. With the laying of the first Atlantic cable in the 1860s, a mistaken notion gained credence. It was thought that a living film on the sea bed consisted of an amorphous sheet of a protein compound, a diffused formless protoplasm. The notion in the nineteenth century that somehow the secret of the origin of life had been penetrated has given way in the twentieth to a more measured observation about a gene pool previously unnoticed. QUESTIONS WITHOUT ANSWERS Perhaps science is, after all, a history of questions. When looking for the origin of the blood, it is inevitable to ask about the embryonic development of blood and the persistence of those governing processes as a means of hemopoiesis into adult life. And it is logical to ask about the nature of a cell that can not only persist for the lifetime of the individual —or somehow pass along its function through some form of cell memory—but can also differentiate into the precursors of all blood cells. What determines the way the stem cell differentiates? A correlate of this asks: Is blood cell differentiation reversible? Can it go both ways—from stem cell to progenitor to specific blood cells back to progenitor and stem? Or is it a one-way street with an end product platelet or macrophage or lymphocyte? And these short-lived? And we would ask about the signi ficance of locating the primordial cell: of what use would it be? And if there exists such a cell, why has it been so difficult to find? 1 2 2 OVER THE ROOFTOPS OF TIME SITES OF ORIGIN In the mid-1800s it was thought that during fetal life the liver was the main blood-forming site. Later it was demonstrated that the first blood cells were formed in the extraembryonic tissues, the area opaca and the yolk sac. The attempt to look at embryonic processes rather than at cell lineages in the adult resulted in later controversy. By 1868, Neumann demonstrated that in the adult organism, the main site of blood cell formation was the bone marrow. As analytical techniques for recognizing the different cell types were not available until Paul Ehrlich applied the use of staining techniques, many questions went unanswered. Ehrlich introduced a dualistic concept...