Health & Medicine / Aging

A couple of years ago I flew to Oklahoma City to meet Ginger Weber. She suffers from an extremely rare genetic condition called Werner syndrome. In the landscape of American health, Ginger is one in a million. Although she and I were born within months of each other—two children of the 1940s baby boom—Ginger’s body has aged much faster than mine. Because of her disorder she is now, in effect, more than 20 years older than I am.

I became interested in Werner syndrome, and its gene, WRN, while researching medical genetics and the Human Genome Project. If DNA could be likened to a revealed scripture, the scientists of the genome project were its scribes, scratching out the sequence of the 3 billion chemical letters that define a human being (the mechanical version). In fact two projects, a public effort and a private venture, had competed to capture the sequence. The primary motivation was to speed the hunt for disease genes and for new drugs to counter them.

In 2000 the rival teams agreed to a tie and prepared to publish their readings of the human genome simultaneously. When the two publications appeared the following year, there was much cap flinging and commentary about the coming transformation of medicine. The competition had whetted everyone’s enthusiasm for the age of the gene, along with creating some anxiety about what the knowledge would mean for individual privacy.

So before driving to Ginger’s house, I stopped at the library of Oklahoma City Community College, which carried Science and Nature, the journals containing the results of the two projects. From one I borrowed a pullout illustration of the human genome. It mapped all the genes known to date. My idea was to show Ginger the location of the Werner syndrome gene, the source of all her pain. I was hoping that this would help break the ice between us.

The Werner gene hadn’t been identified through the Human Genome Project, but it had spun out of the same excitement about genomics and pharmaceutical development during the late 1990s. Indeed, Ginger’s gene had already been patented, traded, and cast aside. Long before I sought her out, I had learned that the great majority of the breakthroughs that are reported in biomedicine are not breakthroughs at all but dazzling dead ends. The light is always at the beginning of the tunnel, rarely at the end.

In 1903 Otto Werner, a German medical student, was introduced to four sisters and brothers who shared the signs and symptoms of an unusual ailment. In their thirties, the siblings were old before their time. Werner, according to an account, “noted they had cataracts, premature graying and loss of hair, as well as skin changes he referred to as scleroderma [excess fibrous tissue].” The student wrote up the cases for his medical dissertation.

Thirty years later, two American doctors described a second instance of Werner syndrome, recognizing it to be an inherited condition. Cases were reported sporadically in the following decades around the world, especially in Japan, where inbreeding had allowed the gene to gain a foothold in some extended families.

The Werner gene—then known to be a single gene, although what genes were exactly was not known—produced characteristic features, including short stature and a squeaky voice. After puberty there was a subtle acceleration of signs of aging, but the disease was not usually noticed until early adulthood, when bones broke unaccountably. Then the affected person, sliding into the crippling conditions of old age, would die of heart failure or cancer or diabetes before reaching 50.

By the 1960s the mechanisms of genes were crudely grasped. Made of long strings of DNA (deoxyribonucleic acid), genes cause proteins to be manufactured, and then proteins run the body. Scientists understood that the Werner gene, being faulty, must make a faulty protein or none at all. But the gene itself, hidden among thousands that were themselves hidden, was a mystery. And the path from the gene to all that could go wrong in the body because of that gene was an even greater puzzle, which remains unanswered today.

By the 1960s, when Ginger was a teenager and still feeling healthy, scientists began to study Werner syndrome for another purpose. They thought the gene might shed light on the prospect of normal human aging. If senescence was happening too fast in the cells of Werner patients, it might mean that a biochemical gas pedal was stuck on the floor. Find the bad gene, the stuck pedal of aging, and you might also find a means to slow down the same process in people who weren’t yet old or sick. A rare genetic flaw could become a model, a research tool, to attack the “disease” of aging in humanity. The pharmaceutical industry has long believed that a pill to increase longevity would be the ultimate blockbuster drug. Thus Americans who never knew Ginger Weber might benefit from her disease.

Ginger lived in Choctaw, a woodsy development east of Oklahoma City. She met me at the door wearing a flowered blouse and pants, leaning on her walker. Her husband was off at work. Isolated by her disease, she’d never had a journalist ask her questions before.

The rooms of the house were kept dark because Ginger, who was recovering from a cornea transplant in one eye, was sensitive to light. In the shadowy living room I noticed mainly that she was very small. Right away she told me, in a high, bright voice, that her red hair was a wig. “I have baby-fine hair, and it was starting to fall out in ’92. That’s when I went to Dr. Rubin,” she said.

Craig Rubin was the geriatric care specialist at the University of Texas Southwestern Medical Center in Dallas who had diagnosed her Werner syndrome and put me in touch with her. The most dangerous sign of Werner, in her case, was premature osteoporosis, a grave loss of bone density. In a research paper, Rubin had listed Ginger’s other physical deficits as they occurred from her teenage years until the time he first saw her at age 43: a maximum height of 4 feet 10 inches; graying and thinning of her hair, beginning in high school; two miscarriages in her late twenties; menopause at 31; cataract surgery in both eyes before 40; a broken left femur [thighbone] at 41 (from “playfully wrestling with her husband”); recent heel surgery; and a progressive loss of tissue from the soles of her feet.