LIFE IN THE LAB
MY MOTHER’S brother, Uncle Paul, died when I was in 12th grade. While my mother was away at the funeral, my father took me out to dinner in Beverly Hills and tried to tell me about my uncle’s illness--all my uncles’ illnesses. My mother’s three brothers had the same rare disorder, he said. It was hereditary: Huntington’s disease. Then, perhaps fearing to tell dire news to someone so young, he assured me that our family would be fine.
Five years later, in 1968, I was vacationing in France when I received a phone call from my father asking me to come home for his 60th birthday. I was suspicious; my father was not sentimental about birthdays. He met me at the airport; my sister Alice arrived shortly.
He took us to his apartment--by this time my mother and he had divorced--and told us a story. It seemed my mother had been on jury duty in downtown Los Angeles. She was a fastidiously neat person, well-dressed and law abiding. She rarely drank. Yet a little before 9 a.m., as she was walking from her car, a police officer stopped her. “Aren’t you ashamed of yourself, being drunk so early in the morning?” he yelled. My mother’s world dissolved.
As gently as he could, my father finally told us the truth about the secret so long hidden in my mother’s family. Mother was dying of Huntington’s disease. It was genetic; Alice and I each had a 50-50 risk of having inherited it. There was no test to determine if we had the gene--only time would tell. If we had it, we could pass it on to our children.
I remember very little of the conversation. Just that my mother was dying and that I had decided I should not have children. I remember that we talked in my father’s bedroom and that we all hugged each other. I know now that my father was terrified that Alice and I would give up our studies in the face of this monumental uncertainty. He says we told him that a 50% chance to be healthy wasn’t so bad. We don’t remember.
ABRAHAM SABIN must have been ill when his youngest child, Leonore, was born. When she was 6, he went to live in a state hospital on Long Island. Seven years later, at age 55, he died. Leonore heard the doctor say he had Huntington’s chorea (as it used to be called). She went to the library and looked it up. Huntington’s chorea, she read in a medical text, was a fatal hereditary neurological disease that destroys the mind and body, causing its victims to writhe uncontrollably, constantly. There was no treatment. The text went on to say, incorrectly, that the disease afflicted only men.
Leonore Sabin was my mother. When she was 15, she went to college, the only one among the children in her family to have done so. Her brothers, Paul and Seymour, started a band that played at the Tavern on the Green and the Hotel Delmonico in New York City. Her oldest brother, Jesse, was a salesman. But Leonore--with her proud brothers’ financial help--earned a master’s degree in biology, with a specialty in genetics, and taught high school in Harlem. In 1936, she met attorney Milton Wexler, who would become her husband and my father.
In 1939, with my mother’s encouragement, my father left the law to earn a Ph.D. in clinical psychology. He became a psychoanalyst and joined the staff of the Menninger foundation in Kansas, where he researched schizophrenia. I was born in 1945, three years after my sister. My mother immersed herself in caring for us. Nothing much disturbed our lives until 1950.
That year, rumors ebbed from New York that Jesse, then 48, was acting oddly. My uncle Jesse had entranced us with fabulous tricks--spinning coins around his fingers and making them magically appear out of his ears, his nose, his pockets. But now the coins dropped to the floor while his fingers danced and twitched.
Paul, age 44, was also having balance and memory problems, and Seymour, 43, had “abnormalities.” Huntington’s was diagnosed at the same time in all three brothers.
The news was catastrophic. My father had known nothing of the disease in my mother’s family. Believing that it only attacked men, my mother had never mentioned it. (I am certain she was also warned to keep it a secret if she wanted to marry.) When my father checked into it, he learned men and women were affected equally.
My mother subsided into depression. My father took action. He realized that he had to support his brothers-in-law financially and plan for the eventuality of illness in his own family. We left Topeka, and he established a private practice in Los Angeles.
When I was little, I adored my mother as someone who gave me unquestioning love and warmth. But as I got older, I knew that something was vitally wrong. She was sad, silent, listless, vague. It was as if some dark subterranean river was taking her away from me. In retrospect, I do not know if her decline was psychological, neurological or both. Perhaps the ominous gene was already beginning to take hold.
In 1964, my parents divorced. My mother was 48 and beyond the age when Huntington’s was expected to appear. As they felt released from the trauma of my uncles’ death and the specter of the disease, problems in their relationship became clear. My mother returned to college, but she felt overwhelmed by the prospect of resuming teaching, and my father continued to support her and take care of almost everything for her.
Then came the diagnosis. At first, we tried to spare her the agony of worrying about her daughters’ chances for the disease. She was told only that she had a progressive disease of unknown origins. My mother appeared to be vastly relieved, but ultimately, we told her the truth. She took it stoically, because, I am sure, she had suspected it all along.
The next decade was a succession of events, one more painful than the next. Once she tried to commit suicide, but my father called an ambulance in time to save her. Then she moved into a succession of nursing homes. The worst of it was watching my mother deteriorate. She was terrified, helpless, depressed and often over-medicated. She said she felt like she was in quicksand, trying desperately to keep from going under.
If she sat relaxed, her fingers kept up a constant motion, as if she were playing a sad tune on a silent piano. Her face twisted, her toes jumped. She needed new shoes constantly; pair after pair were worn down by her incessant movements. When she walked, her left side sagged, and her legs sometimes buckled suddenly, as if she had been hit at the back of her knees.
In one nursing home, she sat in a chair in the narrow space between her bed and the wall. No matter where the chair was put, the force of her continual movements edged it against the wall, until her head bashed into the plaster. We could neither wean her from the chair nor secure it.
We tried to keep her weight up; for some unknown reason, people with Huntington’s disease do better when they are heavy, although their constant motion makes them thin. We kept a little refrigerator in my mother’s room stocked with ice cream, cheese and every fattening, easy-to-eat food we could find. I always brought mountains of cookies and candy. Once she polished off a pound of Turkish delight in half an hour with a grin of mischievous delight. But she never gained weight. I gained weight. I ate to keep her company; I ate to keep from crying.
It was torment when she spoke. At first she sounded drunk. Then her speech became impossible to decipher. I would try to intuit what she might be talking about and give her options from which to choose. If I grasped a word or phrase, I would repeat it so she could feel that she had connected. Toward the end, when she was barely able to make sounds, she suddenly said, clearly, that she liked my sister’s new eyeglass frames.
As she became increasingly ill, I dressed her, carried her, helped her brush her teeth and go to the bathroom, fed her and, mostly, held her and kissed her. Her eyes still haunt me with their sadness and fear. Even possessed by chaotic violent movements, she could be graceful. Until close to the end, she had a sense of humor, and we could sometimes tease her from her worries. She always knew us.
But on May 14, 1978, it was over. Her body was cremated, according to her wish. The funeral was strictly family. We spent the time reading letters she had written in the early days of her marriage. They were cheerful, exuberant and full of intelligence. They re-created the woman who had been vibrant and alive. Now that it was finally over, we could afford to remember her when she was healthy and allow ourselves to feel the enormity of the loss.
MY FATHER’S RESPONSE to calamity is to overcome it, no matter what it takes. Within days of the diagnosis of my mother’s disease in 1968, he decided to take action by forming the Hereditary Disease Foundation. Its first fund-raiser was a concert at the Hollywood Bowl, a tribute to Woody Guthrie, who had died of Huntington’s disease.
The foundation quickly became a central focus for my family, including my mother. We kept her posted on every workshop, every grant funded, every new theory or proposed treatment, every fund-raiser.
But we also pursued full-time careers or education. I became a clinical psychologist, taught at the graduate level and became executive director of the congressionally mandated Huntington’s Disease Commission. My sister earned a doctorate in history, taught at a California college and wrote a biography of Emma Goldman. My father combined a full-time psychoanalytic practice with running the foundation.
He developed a program for the foundation that remains unique in science. It brings together basic and clinical scientists in an interdisciplinary mix for informal workshops. No slides, no speeches, just interaction and brainstorming.
In October, 1979, one of these workshops combined molecular and population geneticists with experts on Huntington’s disease. The participants, including me, heard about how researchers could find genes using DNA markers. This type of research had never been applied to hereditary diseases where the chromosomal assignment of the gene was unknown. If it was to work, it would require studying very large extended families with many members who were sick and healthy.
There have been a few times in my life when I felt certain that something was really right, times when I couldn’t sit still. That was the feeling I had at the end of the workshop--I knew of a family that I thought could eventually lead us to the Huntington’s gene. I had seen them seven years earlier in a filmed report on Huntington’s disease--person after person, all related, all afflicted with Huntington’s, living in villages around Lake Maracaibo in northwestern Venezuela.
We began in earnest in March, 1981. We were a band of about 10 volunteers. We interviewed parents and grandparents and children. We collected blood samples and detailed information on who was related to whom and who had the disease.
On that field trip, and in the trips that have followed--one a year, every March, for 10 years--we have worked primarily in three villages. Almost every house provides shelter to a person affected by or at risk for Huntington’s disease. There are about 150 persons suffering from Huntington’s, and about 3,000 have some degree of risk. We estimate that more than 800 of them will actually die of the disease unless treatment is found.
This Venezuelan kindred--a family tree of more than 10,000 members--is the world’s largest known family with Huntington’s disease. We have been able to trace the illness in the pedigree to a woman who lived in a stilt village in the early 1800s. Where she acquired the deadly gene is unknown.
Thanks to excellent science and good fortune, genetic researchers Jim Gusella and Mike Conneally (and many others it would take pages to name) found a marker for the Huntington’s disease gene just three years after the first trip to Venezuela. It is the critical first step toward finding the problem gene and developing treatments and a cure. And it also means that there is now a fairly accurate pre-symptomatic test that in some families can predict who will die of Huntington’s disease.
FOR MY FAMILY,the breakthrough in Huntington’s disease research has caused an echo of the crisis that confronted us when we first discovered the illness. Taking the test is both an intensely personal, individual decision and a family decision. With each test, each roll of the dice, the family holds its breath. It is important to have counseling to help discover the best course for everyone.
My father has given all the necessary blood samples for my sister and me to be tested, but he would prefer that we not be tested. It would be too devastating for him to know that either of his daughters--or worse, both of them--was destined to repeat the downhill course he witnessed in my mother. My father is not genetically at risk for Huntington’s disease, but he is just as much psychologically at risk as my sister and I. Now, as he works toward a cure, he has hope.
Ultimately, our family’s decision to test or not must remain a private matter. For Alice and me, just thinking through the issues has been both agonizing and instructive. What are the benefits? What are the risks?
Now, when I trip or slur my words or forget a name or can’t balance a checkbook, I wonder if Huntington’s is slithering in to take up residence. But I can talk myself out of it. What if I knew that I had the gene?
If I knew, I could perhaps better plan for the future. But I am more concerned with the present. If the test showed I have the gene, would I continue to feel the happiness, the passion, the occasional ecstasy I feel now? Is the chance of release from Huntington’s worth the risk of losing joy?
There have been times when I have felt inundated by Huntington’s disease, and I have wanted it to play a lesser role in my life. But mostly and ironically, I feel grateful. The struggle against hereditary disease has given me purpose and direction. It has also provided me with a chance to participate in groundbreaking science and, perhaps, the privilege of saving not just the lives of those with Huntington’s disease, but many others as well.