The Gene: An Intimate History - Siddhartha Mukherjee Page 0,190

to genes. Histones may have been chemically modified to record the memory of starvation.

Cell by cell, and organ by organ, the body was reprogrammed for survival. Ultimately, even the germ cells—sperm and egg—were marked (we do not know how, or why, sperm and egg cells carry the memory of a starvation response; perhaps ancient pathways in human DNA record starvation or deprivation in germ cells). When children and grandchildren were born from these sperm and eggs, the embryos may have carried these marks, resulting in alterations in metabolism that remained etched in their genomes decades after the Hongerwinter. Historical memory was thus transformed into cellular memory.

A note of caution: epigenetics is also on the verge of transforming into a dangerous idea. Epigenetic modifications of genes can certainly superpose historical and environmental information on cells and genomes—but this capacity is limited, idiosyncratic, and unpredictable: a parent with an experience of starvation produces children with obesity and overnourishment, while a father with the experience of tuberculosis, say, does not produce a child with an altered response to tuberculosis. Most epigenetic “memories” are the consequence of ancient evolutionary pathways, and cannot be confused with our longing to affix desirable legacies on our children.

As with genetics in the early twentieth century, epigenetics is now being used to justify junk science and enforce stifling definitions of normalcy. Diets, exposures, memories, and therapies that purport to alter heredity are eerily reminiscent of Lysenko’s attempt to “re-educate” wheat using shock therapy. A child’s autism, the result of a genetic mutation, is being backtracked to the intrauterine exposures of his grandparents. Mothers are being asked to minimize anxiety during their pregnancy—lest they taint all their children, and their children, with traumatized mitochondria. Lamarck is being rehabilitated into the new Mendel.

These glib notions about epigenetics should invite skepticism. Environmental information can certainly be etched on the genome. But most of these imprints are recorded as “genetic memories” in the cells and genomes of individual organisms—not carried forward across generations. A man who loses a leg in an accident bears the imprint of that accident in his cells, wounds, and scars—but does not bear children with shortened legs. Nor has the uprooted life of my family seem to have burdened me, or my children, with any wrenching sense of estrangement.

Despite Menelaus’s admonitions, the blood of our fathers is lost in us—and so, fortunately, are their foibles and sins. It is an arrangement that we should celebrate more than rue. Genomes and epigenomes exist to record and transmit likeness, legacy, memory, and history across cells and generations. Mutations, the reassortment of genes, and the erasure of memories counterbalance these forces, enabling unlikeness, variation, monstrosity, genius, and reinvention—and the refulgent possibility of new beginnings, generation upon generation.

It is conceivable that an interplay of genes and epigenes coordinates human embryogenesis. Let us return, yet again, to Morgan’s problem: the creation of a multicellular organism from a one-celled embryo. Seconds after fertilization, a quickening begins in the embryo. Proteins reach into the nucleus of the cell and start flicking genetic switches on and off. A dormant spaceship comes to life. Genes are activated and repressed, and these genes, in turn, encode yet other proteins that activate and repress other genes. A single cell divides to form two, then four, and eight cells. An entire layer of cells forms, then hollows out into the outer skin of a ball. Genes that coordinate metabolism, motility, cell fate, and identity fire “on.” The boiler room warms up. The lights flicker on in the corridors. The intercom crackles alive.

Now a second code stirs to life to ensure that gene expression is locked into place in each cell, enabling each cell to acquire and fix an identity. Chemical marks are selectively added to certain genes and erased from others, modulating the expression of the genes in that cell alone. Methyl groups are inserted and erased, and histones are modified to repress or activate genes.

The embryo unfurls step by step. Primordial segments appear, and cells take their positions along various parts of the embryo. New genes are activated that command subroutines to grow limbs and organs, and more chemical marks are appended on the genomes of individual cells. Cells are added to create organs and structures—forelegs, hind legs, muscles, kidneys, bones, eyes. Some cells die a programmed death. Genes that maintain function, metabolism, and repair are turned on. An organism emerges from a cell.

Do not be lulled by that description. Do not, gentle reader, be tempted to think—“My goodness, what