Blood Matters

by Masha Gessen

  There is a black-and-white picture of me at the age of perhaps two months. My mother is holding me, her lips buried in the black down on my head, and she has that look of being desperately tired and profoundly in love, a look—or, rather, a state—I recognize. This is the last evidence that we had this connection. When I walked into her hospital room at Boston’s Brigham and Women’s Hospital in August 1990, she pointed with her chin toward the flatness under her gown and said, “I fed you with that breast.” She sounded like she was saying something one said in such situations. I mumbled something noncommittal, which is to say, unfeeling: I felt nothing.

  Fourteen years later, I sat at a large table with women who carried my mutation. The hospital where my mother had her mastectomy and where I now went for my breast MRIs was across the street. The dozen women around the table dined on takeout and talked about cancer as a social worker looked on. She was there to help us talk to one another and also, this being a research institution, to observe how this newly isolated breed—women who knew they carried a cancer-causing mutation—would behave when placed together. I tried not to draw attention to myself as I looked around the room. I looked at noses, eyebrows, hands. The women looked nothing like me, but many of them had the thick postchemo hair, the brittle postchemo skin, and the protruding breast prostheses that reminded me of my mother. Other than that, our genetic commonality was invisible.

  My daughter will go on in the world with feet and eyebrows that are replicas of mine, a stubbornness just like mine, and the habit—my habit—of scrunching up her face when doing something that requires great concentration, such as coloring within the lines. Most important, she will carry with her the memory of me, perhaps even the physical sense of me. That physical awareness is the essential element of security. Whatever trace of my mother I carried—even if it was the mere knowledge of her existence—had kept me from feeling mortal as long as she was alive. When I awoke on the morning of her death, I felt a fear that has not left me since. For months after I learned of my mutation, I would think about this in the sleepless early mornings, when my daughter pressed her hot heels into the small of my back, and I knew I was the only thing that protected her from the cold wind of fear and freedom that came into the room through the open balcony door. Then she would tap me on the shoulder and ask me to turn around so she could hold my breasts.

  ***

  One of the women who carried a BRCA mutation started a Web site to help women share information about risks and possible remedies. I found myself checking the message boards several times a day. Women talked about surgeries, drugs, and screening procedures. The level of detail and the depth of knowledge were astonishing: Even as patient communities go, this was an extraordinarily educated and motivated one.

  Whenever I pulled out my cancer-center patient card—whether to schedule an appointment through my regular health center or to park in a hospital lot—I received a recognizable sympathy look, the sort that says, “So young. So tragic. So frightening.” I felt a bit like an impostor: I did not have cancer. I had come to realize that my admission to the cancer caste, conditional as it was, was but a temporary substitute for the yet-unrecognized group of which I had become a member. It was not quite a secret society, but it did live, invisibly, by a set of rules different from those of the rest of the world. In this society, people become privy to the information contained in their genes and reshape their bodies—and their fates—accordingly. The rules by which this society lives are an approximation, albeit a very crude one, of the rules by which my daughter’s generation will run its life.

  Understanding my accidental role in this rehearsal of the future was part of what made me want to write this book. But there was something else, too. The frontier women who were cutting off their breasts to spite their genes were just the most visible and vocal expression of the transformation in our understanding of ourselves. I belong to a generation that grew up believing we were shaped by love, care, or lack of it—or perhaps even the number of books on our parents’ bookshelves. But we will go to our graves believing that it is a combination of letters in our genetic code that determines how we get there, and when. Our concept of the stuff we are made of will have undergone fundamental changes. I got a glimpse of that when I was looking around that room at my fellow mutants, and again and again in the process of writing this book, as I looked at myself, my biological daughter, and my adopted son. I was transported to a new era, a future that will rest on a different understanding not only of what causes things to go wrong in human beings but of what makes a human being in the first place, and what connects any one of us to any other.

  Chapter 2

  The Four Mothers of Jews

  ONCE YOU JOIN a secret society, you find fellow members everywhere. After I wrote a series of articles on my mutation for Slate I began to get letters from long-lost friends, friends of friends, and people who thought we should be friends. Women whom I met professionally would confess their genetic information to me. In a colleague’s office in New York, I was pulled roughly aside to hear, “I am BRCA, too”—or was it “BRCA2”? Even though there were only two of us in the office, for a moment I had a hard time identifying the source of the whisper, so sharply did it break with the context of the conversation we had been having. Once I got my bearings, I realized I was staring at my interlocutor’s chest, which was perfectly flat.

  For the most part, I welcomed the communication: The same impulse that moved people to write or call led me to respond enthusiastically. Each new flesh-and-blood acquaintance made my predicament seem less extreme, and many shared useful information. I also found myself relentlessly looking for clues that would make sense of my situation. One of my newfound friends mentioned that her family hailed from the Polish city of Bialystok. My paternal grandmother was born in Bialystok, and I found myself wondering if I had inherited the mutation from my father, and he from his mother, who was alive and cancer-free at eighty-three. This would be good news if it were true: If she could carry the mutation and not get sick, my odds of developing cancer would be ratcheted down. The mechanism by which my mutation causes cancer is unclear, but some families seem to do better with it than others. Whether this is because of genes or environment is impossible to say: Families tend to share both.

  But, of course, the Bialystok lead was a red herring. Bialystok was a major center of European Jewish life before World War II. Statistically, 1 percent of the Jews of Bialystok would have carried the mutation. It seems my friend’s family had it and my paternal grandmother did not.

  A brighter ray of hope appeared when my maternal grandmother—eighty-six and complaining only of arthritis—told me that her mother had had her ovaries removed before the age of fifty. Why? “She had an inflammation.” Back when my great-grandmother was ill, cancer was a word rarely uttered: In the family it may well have taken on the name “inflammation.” In some ways, this imagined lineage for my mutation had even greater appeal. My grandmother was a very fit, very active, and unfailingly happy person—very much unlike my mother but, I liked to think, rather like me. It must have been my grandmother’s skill at extracting joy from life, combined with her physical activity—she had recently given up her bicycle but still insisted on cross-country skiing in winter—that allowed her to beat the genetic odds. I was also possessed of something of a manic personality and exercised obsessively. Had the ability to defeat genetic fate skipped a generation? The idea fit my internal understanding of genetics perfectly. I should note that, inasmuch as they are genetically determined, traits do not, of course, skip generations: They are inherited directly or not at all. Still, the idea that exercise and fitness could moderate the risk of cancer even in mutation carriers was not entirely without merit; it is just that the adjustment was small, and my statistical risk of developing cancer would remain many times that of someone who did not carry an altered gene.

  I stopped chasing after rays of hope after Natasha, my mother’s first cousin, got the test. I had called her when
I was about to be tested, to check which kind of cancer had killed her mother—yes, it was ovarian—and got in touch again a few months after getting my own results. Natasha’s test came back positive for the same mutation as mine, proving that in our family’s case the simplest and most obvious solution fit the puzzle best. The mutation must have gone back to my great-grandfather, who died of some sort of cancer in his sixties. That death too may have been related to the mutation, which raises the risk of all cancers, including prostate, pancreatic, stomach, and colon—though the risk is not nearly as high as the risk of breast and ovarian cancer in the women who carry the mutation. My great-grandfather broke the fifty-fifty rule by passing the mutation on to both of his children: his son, who was killed in the war at the age of twenty-two, and his daughter, who died of ovarian cancer at fifty-two. Each of them had a child, both of whom in turn inherited the mutation. They were my mother, who died at forty-nine, and Natasha, who was apparently healthy at fifty-three, which was wonderful but hardly statistically significant. The evidence seemed to say that I came from the sort of family where female mutation carriers did develop cancer—and tended to die of it.

  ***

  Natasha had been tested at Hadassah, the large teaching hospital that sits on a mountain overlooking Jerusalem. For a major international medical and research center, the accoutrements seem a bit too modest: The offices are small, the waiting areas virtually nonexistent, the furniture scuffed, the ceilings peeling, and the handouts badly xeroxed. To get to the genetics clinic, one has to pass a metal detector, present one’s bag for inspection, and wind through a couple of labyrinthine hallways. A plain white sheet of paper lists the conditions for which prenatal tests are offered. The list is split into three categories: conditions frequently found among Ashkenazi Jews, among Sephardic Jews, and among Yemenites. The last category contains just a few disorders, the Sephardic list comprises perhaps a dozen, and more than half the sheet of paper is taken up by tests available to the Ashkenazim. Michal Sagi, the young woman who ran the genetics program at Hadassah when I interviewed her in 2005, said, smiling, “Some of the Yemenites look at this sheet and say, Ah, the Ashkenazim are so sickly!’”

  We both laughed. The Ashkenazim are just better studied than other Israeli populations, and other Middle Eastern population groups appear to have many common genetic conditions of their own. Still, the question of why the Ashkenazim are so sickly has occupied scientists for some time.

  There are several genetic conditions that are unusually common among Ashkenazi Jews. Most of these are recessive traits, meaning that a person with a single altered copy of the gene has no symptoms but has a fifty-fifty chance of passing the gene to a child. A child who inherits two mutant copies—a one-in-four probability if both parents happen to be carriers—will get sick. Two explanations for the prevalence of these recessive traits compete for primacy in science. One explanation is selective advantage: The theory suggests that a single copy of the affected gene may offer protection against another disease. The best-known case of selective advantage is the genetic mutation that causes sickle-cell anemia in a person with two copies of the mutant gene but offers protection against malaria in people with just one copy. The same may be true of “Jewish diseases”: a person with two copies of a “bad” Tay-Sachs gene, for example, will die in childhood, but perhaps a person with one copy will enjoy protection against tuberculosis and therefore survive longer than many of his compatriots and have a chance to have more children, thereby ensuring that the gene gets passed along.

  The other possible explanation for the high incidence of recessive conditions is bad luck. The professional term is one of the most evocative in all of science: genetic drift. The theory says, in essence, that not everything evolves in accordance with the laws of natural selection: Sometimes things just happen. The smaller the population, the more likely things are to just go awry. The classic explanation involves a coin toss. If you toss a coin a thousand times, you are virtually guaranteed to see a fifty-fifty split between the number of times it lands heads up and tails up. But if your sample is drastically smaller—if, say, you toss a coin ten times—you are likely to see a statistically lopsided picture: seven heads, for example, versus three tails. By the logic of genetic drift, a mutation can take hold in a population simply because the population is very small. Say it originates with a few founder families, or even just one. If the person or persons with the mutation do not have much success reproducing, the mutation will get washed out. But if they happen to be fertile, or rich, or both, they may manage to have many children who will grow to adulthood and make up a significant group—half of them carrying the mutation—within the small population.

  A good analogy for the concept of genetic drift is what happens to surnames. Surnames are inherited patrilineally, which means that generally only sons will carry on a family’s last name. Since the chances of having a boy child are roughly fifty-fifty, the chances of passing on one’s surname are equivalent to the chances of passing on a genetic trait. My great-great-grandfather had eight children, all of whom carried the last name Gessen. Two sons died young, two others never had children, two daughters had children who carried their husbands’ last names, but my great-grandfather had four children named Gessen, and one of his sisters had an out-of-wedlock son who was also a Gessen. In other words, the last name suffered some losses in that generation but still had a decent chance to survive in the population. My great-uncle—the out-of-wedlock Gessen—had epilepsy and decided, in accordance with Jewish tradition (if not with genetic logic) forbidding epileptics from marrying lest the illness be passed on, never to have children of his own. He married a woman who already had children, whom he raised as his own. He died surrounded by grandchildren and even a great-grandchild, none of whom carried the name Gessen. My great-grandfather’s two sons, on the other hand, not only survived World War II but had six children between them, three of them male. On the whole, this was not great going: The number of Gessens in this generation grew by just one person. In the following generation, my uncle and my father’s cousin had two daughters each: The chances that these girls will carry on the Gessen name are negligible. My father had three sons, and his sister had an out-of-wedlock son who got the Gessen name, which makes a total of four Gessen males in my generation, but so far all of them have failed to reproduce. As it happens, the only person in my children’s generation who is poised to pass on the surname is my son, Vova, who is adopted and got his surname the way one cannot get a gene: by court order. If the Gessen name were a genetic trait, it would be on its way out. At the same time, I have a couple of dozen cousins descendant from the Gessen line; if things had gone a little differently in terms of sex distribution and reproductive patterns, Vova could have four or five dozen cousins named Gessen, rather than none. This is the essence of genetic drift.

  ***

  The most frightening of the so-called Jewish diseases are Niemann-Pick, Canavan, Gaucher’s, and Tay-Sachs. The last is the best-known and one of the most common: One in twenty-seven Ashkenazi Jews is a carrier. A baby born with two copies of the mutant gene lacks an enzyme necessary for breaking down fatty substances in the brain and nerve cells. These substances build up, and around the age of six months begin blocking the functioning of the baby’s brain and central nervous system: a baby that seemed healthy suddenly stops smiling, turning over, and grasping toys. The child degenerates, becoming blind, paralyzed, and totally unresponsive, and usually dies before the age of five.

  One in thirty-seven Ashkenazi Jews is a carrier of the gene for Canavan disease. Affected babies lack a different enzyme, which leads to the buildup of a particular acid that in turn destroys myelin, or “white matter,” in the brain. Symptoms appear between three and six months of age; the baby becomes developmentally delayed and may also go blind. The children die before the age of ten.

  Niemann-Pick is another enzyme deficiency that leads to the buildup of a fatty substance—in the brain, liver, spleen, and lymph nodes.
Babies become blind and disfigured and usually die before the age of two. One in seventy-five Ashkenazim is a carrier.

  Gaucher’s is also an enzyme deficiency that leads to the buildup of another fatty substance, which can cause symptoms ranging from mild to severe, including anemia, fatigue, and bleeding. Unlike the other enzyme deficiencies, it is not universally fatal, and treatment is available. One in fourteen Ashkenazi Jews is a carrier of the Gaucher’s mutation.

  None of these conditions is unique to Jews, but they are more common among the Ashkenazim than in any other population. The fact that they share some features—all are enzyme deficiencies, and all but Canavan are what are called lipid-storage diseases—has long led scientists to suspect that this is no accident. Neither bad luck nor genetic drift can explain the emergence of different mutations (each of the conditions can result from one of several) that affect different genes but cause similar processes to occur in the body. The explanation must lie with selective advantage—but what sort of selective advantage could it have conveyed?

  In 2005 three Utah researchers published a study suggesting that Jews are so sickly because they are so smart. Ashkenazi Jews have the highest average IQ of any ethnic group that has had its IQ measured as a group. That does not mean that there are no Ashkenazi Jews of average or below-average intelligence. Indeed, the difference in mean IQ is not huge: The average Ashkenazi IQ is 108 to 115, while the average IQ in general is, by definition, 100. Again, this does not mean that all Ashkenazi Jews are smarter than all gentiles. What it does mean is that, proportionately, there are many more very intelligent people among Ashkenazi Jews than among other groups. This high general intelligence is frequently realized in measurable intellectual achievement. Ashkenazi Jews, who constitute less than 3 percent of the U.S. population, account for 37 percent of the winners of the U.S. National Medal of Science, 25 percent of American Nobel Prize winners in literature, and 40 percent of American Nobel Prize winners in science and economics. Ashkenazi achievement in the visual arts and architecture, on the other hand, does not stand out—and Ashkenazi Jews tend to score slightly lower, on average, than other Europeans on tests of spatiovisual ability. Indeed, the gap between Ashkenazi IQ and spatiovisual scores is one of the odd features of this ethnic group.