During her first encounter with cancer, Susan Sontag described a tumor as a “demonic pregnancy.” “This lump is alive,” she wrote in “Illness as Metaphor,” “a fetus with its own will.” She could hardly know that the comparison would become more than a figure of speech.
Since the book was published in 1978, scientists have been finding that the same genes that guide fetal cells as they multiply, migrate and create a newborn child are also among the primary drivers of cancer. Once the baby is born, the genes step back and take on other roles. But through decades of random mutations, old embryological memories can be awakened and distorted. What is born this time is a tumor.
“Cancer proceeds by a science-fiction scenario,” Sontag wrote, invoking movies like “Invasion of the Body Snatchers” and “The Blob.” When Ridley Scott’s “Alien” appeared at the cinema in 1979, his imaginary space creatures, hatching their eggs inside human bodies, made her comparisons seem all the more gruesome.
There is no need, of course, for an alien impregnation. Cancer can be provoked by a carcinogen or a hormonal imbalance — or just a senseless, spontaneous mutation. Tipped from its equilibrium, a cell begins multiplying faster than it should. Two cells become four, then eight, then 16. Sontag’s demonic pregnancy, like “Rosemary’s Baby,” stirs to life.
Rough similarities between the growth of a tumor and the gestation of an embryo were first suggested more than a century ago. But no one could have guessed that the parallels would turn out to be so precise.
Consider the gene SHH. The name is short for sonic hedgehog. (Hedgehog genes were discovered in fruit flies and when mutated they cause the larvae to be covered with a profusion of bristles.) In a human embryo, sonic hedgehog is involved with establishing the bilateral symmetry of the brain, skeleton and other organs. Later in life it can run amok, interacting with genes like SMO (for smoothened — another fruit fly derivation) to bring on a human brain cancer called medulloblastoma and a skin cancer called basal cell carcinoma.
Step by step, these and other genes play powerful roles in both creating and subverting a human life. In the early days of pregnancy, the primitive embryo — this rapidly dividing glob of cells — eats out a spot in the uterine lining using corrosive enzymes called proteases. Then it holds tight for the duration with the help of proteins like integrin, a kind of biological glue. Both types of molecules are also used by a cancer as it digs in and adheres to its berth.
Whether confronted by a tumor or a healthy pregnancy, the immune system reacts with alarm. To keep from being rejected like a mismatched organ transplant, the budding embryo sends chemical signals to quell the counterattack. Cancer cells engage in the same subterfuge.
As the embryo becomes established it secretes other enzymes, and these lead to the sprouting of blood vessels — a nourishing connection to the mother’s circulatory system. This process, called angiogenesis, is also exploited by a tumor as it fuels its growth by creating its own parasitic blood supply.
After hooking into the bloodstream, cancer seeds can spread to other parts of the body and sprout new malignancies. The process, called metastasis, appears to be driven by the same mechanism used in the embryo to dispatch freshly created cells to their proper locations.
In this complex metamorphosis, epithelial cells — the kind that stick together in sheets to form bodily tissues — are converted into loosely organized cells called mesenchyme. In this state they are free to move where they are needed to make body parts. Once they arrive they can regroup to form tissues and organs.
In a healthy embryo, this is an orderly affair. In cancer it leads not to new organs but to more tumors.
There is a point where cancer parts ways with its legacy from embryogenesis. Crucial to the development of a fetus is a phenomenon called apoptosis. The name, derived from ancient Greek, refers to the falling away of leaves from a tree or petals from a flower. Another name for it is cellular suicide.
In the burgeoning of cells that occurs during gestation, many are superfluous, and apoptosis encourages them to die. From a weblike flipper, distinguishable fingers emerge like sculpture from rock.
Once the new being is pushed into the world, apoptosis continues to be involved. Normal cells know to die when they become badly deranged. But an aspiring cancer soon learns how to wire around the self-destruct button. Spinning further out of control, it goes on to produce the mockery of a fetus called a tumor.
Confronted by the roiling chemical confusion inside a living cell, metaphors — the comparison of the strange to the familiar — can help scientists focus, separating signals from noise. But they can also beguile and mislead.
Sontag’s aim in her book was to explore how the language we invent for illness reflects society’s own diseases — its fairy-tale attitudes toward death, its addiction to unrestrained growth, consumption and violence.
Though she didn’t say so in the book, her own treatment for breast cancer involved a radical mastectomy and intense chemical warfare to stop the invader. In an optimistic moment she hoped that clinical advances would lead to a softening of the militaristic imagery as gentler therapies were developed, ones that stimulate the body’s own natural defenses.
Her enthusiasm was premature. Immune system therapy is recently showing renewed signs of promise. But when Sontag was given, later in life, a diagnosis of a cancer of the uterus and then — the one that killed her in 2004 — a cancer of the blood, the old warlike treatments remained the norm. For all the advances in understanding what cancer is like on a cellular level, that is still the reality today.
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