Sixty thousand years ago, at a site called Shanidar, in what is now Iraq, the body of a Neanderthal man was carefully buried in a cave. Lying on his left side, head toward the west, on a bed of evergreen boughs and covered in flowers, the man would later be identified through microscopic analysis of the surviving pollens. The flowers were from eight different species and the arrangement was not accidental: There was a purpose to the burial process. It is the earliest memorial celebration of life and mourning of death of which we know.
Behind every one of the 6.3 billion people now living lie seventeen others in the ground. Every organism that has ever lived has died. And now that the Neanderthals are extinct, as far as we know we are the only species aware of its own mortality. Thus we are faced with the question that has haunted everyone who has thought about this uncomfortable fact of life: Why are we here?
I started thinking hard about the brevity of life and the need to find meaning in it in 1992, when my mother was diagnosed with a brain tumor. For some time, she had been acting strangely confused a lot of the time, disoriented, and emotionally unstable. My folks had just been dealt a significant financial blow, so I thought perhaps the fear of being destitute, for a woman who grew up during the Depression, had triggered the erratic behavior. I spent countless hours talking to her, as did her sister, her friends, and my dad. I escorted her on long walks in hopes that physical exercise might release some mood-elevating endorphins.
Months passed with no sign of improvement, however, so we took her to a psychiatrist in Pasadena, California, who diagnosed depression and prescribed medication. I was skeptical and asked for a second opinion, perhaps from a neurologist.
It was October, the middle of the Bush-Clinton-Perot presidential debates, but when the neurologist asked my mom who was running, my mom didn't know. Minutes later, she was wheeled in for a computed tomography (CT) scan. I nearly fainted when I saw the results: A massive tumor filled the front half of the left side of her skull, smashing her neurons against the back of her brain case. My voice shaky, I explained to her what was going on, and that she would need major surgery. Because her brain was squashed and not processing clearly, she just shrugged and said quietly, "OK."
My mom's tumor was a meningioma-originating on the meninges, the protective lining of the brain. Most meningioma tumors are successfully resected, and indeed, within days of my mom's surgery, her brain filled the hole. She was back to her bright and cheery self.
Unfortunately, the recovery was short-lived. Within months of the initial surgery, two new tumors appeared. Fortunately, they were within reach of the surgeon's scalpel. But their removal in March 1993 was followed by the emergence of other tumors and the need for additional craniotomies, one that July and another in September 1994.
My mother's experience seemed to support Harvard Medical School surgeon Judah Folkman's controversial angiogenesis theory of cancer, developed in the 1960s. Angiogenesis is the formation and differentiation of blood vessels. Folkman noticed that tumors planted in isolated organs in glass chambers all stopped growing at a certain size, and deduced that a lack of blood vessels prevented their continued development. In a 1971 paper for the New England Journal of Medicine, he outlined the tenets of his theory: Blood vessels in tumors are new, which means the tumors had to recruit them via an agent called "tumor angiogenesis factor," or TAF. Since TAF draws blood vessels to the tumor, if the production of TAF is stopped, the tumor ceases to grow.
By the 1980s, Folkman had discovered a number of angiogenesis inhibitors. In the late 1990s, endostatin and angiostatin were found to be highly effective retardants of mice tumors. Today, about twenty different compounds are being tested for their anti-angiogenesis capacity, although none has been consistently effective in attenuating tumor growth in humans.
It was Folkman's belief that tumors secrete their own angiogenesis inhibitors, preventing other tumors from drawing blood vessels to them and growing. Remove the dominant tumor, however, and you eliminate the inhibitors, allowing other dormant tumors to spring to life. I had always thought of tumors as somehow not as bad as cancer. In fact, tumors may be benign or malignant-encapsulated and contained versus tentacled and spreading.
After four craniotomies in two years, my mom's recurring tumor was upgraded to an invasive malignant meningioma. It was even more invasive than her physicians realized: In 1999, she developed two tumors in her lungs. Could the meningioma have migrated out of her brain? Impossible, we were told. There was no known case of such a migration, whether the tumor was benign or malignant. By Folkman's theory, however, this was possible. A tumor contains so many micro blood vessels that single cells could escape the mass and invade the general circulatory system.
This scenario was given more credence by Avrum Bluming, a practicing medical oncologist and founder of Los Angeles Free-Net, a nonprofit organization providing extensive medical information online. I met Bluming by chance, at a dinner party hosted by a mutual friend where, after recounting my mom's plight, he told me of a paper that documented two cases of a meningioma migrating out of the brain. How is it, I wondered, that my mom's oncologists and surgeons, among thebest in the world and all remarkably humane throughout this ordeal, did not know about these cases? Had it not been for my fortuitous conversation with Bluming, perhaps I would never have learned of them either.
Lung surgery in October 1999, followed by a fifth craniotomy that permanently removed an infected skull plate, gave us temporary relief-but before long, the meningioma was on the march again. By this time, my mother had endured not only the five craniotomies, but also four gamma-knife radiosurgery treatments, in which a powerful machine resembling a nineteenth-century phrenology contraption fits tightly over the head and radiation zeros in on the cancer from all sides. We were finally told that the risks of additional surgery and radiation outweighed the benefits. There was nothing more to be done.
In spite of my unwavering ideological commitment to science, I could not accept the doctor's pronouncement. I turned to experimental drugs for my mother, and with the help of Bluming himself, decided we would try mifepristone, better known as RU-486, the so-called "abortion pill." RU-486 was illegal at the time, so we had to go through a Washington, D.C.-based women's rights advocacy group, the Feminist Majority Foundation's Mifepristone Compassionate Use Program, to obtain treatment dosages. A small-sample study suggested the drug might retard the growth of tumors. It did not for my mother, however, so we tried temozolomide, a drug designed to prevent the replication of cells that divide rapidly, the way cancer cells do.
Nothing we tried was able to halt the inexorable march of the cancer that migrated into the middle of mom's brain, where it could not be resected or radiated. The magnetic resonance imaging (MRI) diagnostic report was sterile but bone chilling: "Again identified is an approximately 2.5-by-4.0-centimeter mass in the right frontal lobe involving the corpus callosum. A similarly sized irregular mass is again identified in the left frontal lobe."