At the end of the day, George Smith drives to a dream house in Hidden Hills, a celebrity-filled enclave north of Los Angeles. Just past the security gate await his gardens, his swimming pool, his tennis court, his horses. Inside, a collection of modern art--by Hockney, Rivers, Bennevente--glows under tiny spotlights. A personal trainer prepares for his workout. This life is so much more than a shopkeeper's son ever imagined. And right now it means nothing. Smith's head is pounding as he opens the front door. He usually looks 10 years younger than his 64 years, exuding enormous energy. But today his linebacker-size shoulders slump. His tie is askew and his face is ashen. "How's Becca?" he asks. "It's probably just a cold," his wife, Pamela, answers. George falls silent. He takes off his coat and sighs. <o:p</o:p "I need some Advil," he says, disappearing toward the kitchen. <o:p</o:p A tension headache in this household is allowed now and then. Every day they fight a battle for life against an enemy with no soul. Among the demons that can be produced in the human genome, ataxia-telangiectasia--A-T for short--is one of the most sadistic. At birth, children with the hereditary disease are as bright and healthy as any. But over time they grow wobbly and frail. Canes are followed by walkers and wheelchairs. Uncooperative eye muscles steal the pleasure, and escape, of reading. Speech becomes garbled. Many children with A-T age prematurely, looking wizened before they are 20. Immune systems weaken. Most die of cancer or infection before 30. <o:p</o:p The discovery in 1982 that her daughter, Rebecca, then 4 1/2, had A-T struck Pam "like I had actually been hit in the stomach." The Smiths soon learned that A-T is an "orphan" disease, a disorder so rare that few scientists were interested in finding a cure. The number of American children known to have A-T is in the hundreds, not thousands. It never has attracted big research grants. <o:p</o:p *************************************************************************** <o:p</o:p In 1980, two years before anyone noticed the little imbalance in Becca Smith's gait, physician Richard Gatti left a promising career path to dedicate himself to the study of A-T. Help was scarce, and so was money. Just a handful of scientists worldwide were devoting any time to the disease. <o:p</o:p As a young doctor, Gatti had worked in Minnesota under Robert Good, a pioneer in the field of immunology. Gatti was part of a team that established a link between immune deficiencies and cancer, and, in 1968, he conducted the first successful human donor bone-marrow transplant in history. (The procedure is now commonly used to bolster the immune system.) Like all young academic stars, he was looking for an opening, a promising but neglected area of research where he could distinguish himself. Then he encountered a group of children--all with cancers not usually seen in the young and all afflicted with A-T. Gatti was intrigued. The gene that caused A-T was obviously an important one. A-T affects so many systems in the body--immunology, neurology, reproduction, even aging--that any clues to its cause could open the door to understanding a host of diseases, from cancer to Alzheimer's. <o:p</o:p Gatti also was deeply moved by the suffering of the children and their families. "I didn't pick A-T. The children and the disease picked me," Gatti muses. There was an element of destiny, too, he says. As a boy he had been touched by the tale of three aunts, his father's sisters, who suffered from a form of ataxia that had overcome them as young adults. One, a prima ballerina in her teens, was wheelchair-bound by 28. <o:p</o:p When Gatti decided to take the risk of retreating to a remote corner of science, he had no idea of the struggle that lay ahead. He spent four frustrating years coping with little money and even less professional support. Gatti's first love had been piano, and he devoted many years to it--even training at Juilliard--before going into medicine. Now he had given years to an obscure cause. The rewards had been negligible and the price had been high. He was deeply depressed. His marriage was in serious trouble because his wife had finally given up competing with the lab for his attention. <o:p</o:p Then this: a letter from the National Institutes of Health, from which Gatti had sought funding. The letter praised Gatti's work but denied him money because, in the view of officials there, he was unlikely to reach his goal of isolating the gene responsible for A-T. "The NIH letter said my work was a 'Herculean task,' and they implied I was never going to complete it. I really was obscure. Everyone thought I was wrong to put so much into this." <o:p</o:p Without the NIH money, the future of his lab was in doubt. <o:p</o:p *****************************************************************************<o:p</o:p George Smith was constitutionally unable to shrink from the challenge of his daughter's disease in 1984. His life experiences simply wouldn't allow it. <o:p</o:p Smith was raised in the gritty Rego Park neighborhood of Queens, N.Y. His mother was the daughter of an orthodox rabbi who had barely been able to feed and clothe his children. George's parents wanted more for their son, and they made their expectations clear. "There was a lot of pressure on me," he recalls. "I was expected to be successful, and I really learned that lesson very well." <o:p</o:p As a boy, Smith showed extraordinary aptitude for numbers, which came in handy as he obsessed over the stats of his favorite New York ballplayers. After his family moved to Los Angeles in 1948, he parlayed his skill with numbers into an engineering degree at UCLA before moving on to Harvard Business School. He became a real estate banker. <o:p</o:p Through several booms and busts in California real estate, Smith stuck to a sleep-on-the-office-sofa work ethic, eventually creating one of the largest deal-making firms in the West. Today George Smith Partners puts financing together for complex, multimillion-dollar housing, commercial and industrial developments on the West Coast. <o:p</o:p When Smith learned that his daughter had A-T, he behaved as he always had when dealing with seemingly insurmountable problems. "I contacted everyone I knew who might have some idea of what is going on with medical research. No one knew much of anything. But I did eventually network my way to Dr. Michael Swift in North Carolina, who was working on A-T." Smith soon learned, however, that Swift was studying the patterns of A-T's occurrence in families, not working to find a cure. <o:p</o:p Desperate, the Smiths flew to the NIH in Washington, D.C., where they heard more bad news. The NIH had provided precisely zero dollars to fund A-T research, and the institution had little interest in the disease. Before the Smiths left, however, one of the people they met asked if they had checked for researchers at UCLA. After all, they were told, Dr. Elena Boder, who originally named A-T back in the 1950s, had been affiliated with UCLA. Maybe someone at the school was still interested. <o:p</o:p Someone was. Gatti had moved to Los Angeles years earlier and was running his tiny lab at UCLA Medical Center. <o:p</o:p ***************************************************************************Looking at Becca, 21, seated on the bed in her room, it is possible to forget her disability. She is pretty, with blue-gray eyes and a perfect, shy smile. It is only when she must command her muscles--to walk, or talk, or pick something up--that Becca seems different. <o:p</o:p Her deterioration has been slow but relentless. Still, Becca's health is better than most. Every few months, it seems, an A-T child the family knows gets pneumonia, or cancer, or dies. Becca exercises to maintain her muscles and coordination. She eats carefully and gets ample rest. <o:p</o:p But vigilance and good health do not mean an escape from A-T. For most of her life Becca has known she is different from other children, and she has imagined the future in small measures. "I do not have this the worst," she says. "For me, the big thing is the balance problem. But I can still be with my family and communicate. Of course, I have always known that I am different. I have tried not to dwell on it. But how could I not know?" <o:p</o:p It's the kind of difference that children never overlook. "In middle school we had an assembly, an open forum, for the entire school where they could ask questions about A-T and me," Becca recalls. "My father came and he did a lot of the talking. The real thing we wanted people to understand is that they could treat me like any other kid." <o:p</o:p Her brother, Matthew, 17, certainly does. He says he's never thought about Becca dying because she doesn't act as if she's ill. Becca's need to be treated like any other person, even as her disease made her ever-more different, creates a paradox. She needs help with such mundane tasks as dressing and bathing, and every trip out involves a wheelchair and a search for special parking spaces. At the same time, as the Smiths work doggedly to raise money for a cure, at home they talk very little about the disease, or the future. <o:p</o:p "The idea is for Becca to go as far as her abilities, especially her mind, can go," Pam Smith says. She learned the depth of her daughter's determination when Becca was in elementary school and came home declaring she would play the recorder in a school recital. Pam had visions of her daughter falling, or being unable to control the instrument and suffering the jeers of her classmates. Becca saw it differently, and she hid under the kitchen table until her mother agreed to let her perform. <o:p</o:p At the recital, Becca propped herself against a chair and played "Twinkle, Twinkle, Little Star" flawlessly. Pam Smith watched in tears. Since then she has helped make other academic achievements possible for Becca, including her graduating from high school with honors and taking classes at Moorpark Community College. <o:p</o:p This spring Pam and Becca rented a store on the south side of Ventura Boulevard in Woodland Hills. A little remodeling, most of it donated by local craftsmen, and barely used clothes from scores of wealthy supporters turned the space into Becca's Chic Boutique, a designer resale shop. Profits go to A-T research, but the boutique also provides an outlet for Becca's creativity and energy. She's there almost all the time, running the place from her wheelchair, parked behind a specially made customer counter. <o:p</o:p "I just keep going," Becca says. "I don't worry too much about me. But lately I have worried more about my mom dying. I'm so dependent on her. Other kids don't need someone to help them bathe and get dressed. I do." <o:p</o:p ***************************************************************************** The Richard Gatti who met George and Pam Smith for lunch at the UCLA Faculty Club in 1984 had flecks of gray in his curly dark hair and lines of age and anxiety creeping across his face. The NIH had just denied his funding. "I remember that as I went to meet George for the first time I was thinking about the NIH letter," he says. Over their buffet meal, the two men bonded quickly, discovering they had grown up just a few miles apart in New York. As youngsters, they had listened to the same ballgames on the radio, nursed similar dreams of success. <o:p</o:p Gatti explained the research that had established the cause of A-T as an inherited mutant gene. He had conducted important elements of this research, including traveling to an Amish community in Pennsylvania where A-T was prevalent to coax blood samples from farmers. He also explained that the A-T gene seemed to be involved in the control of the immune system. He believed that it signaled the body to repair damaged DNA, which otherwise might cause cancer. <o:p</o:p If he could find the A-T gene, he might then find ways to overcome the mutation that caused Becca's disease. Along the way, he might also help millions of patients suffering from various forms of cancer. <o:p</o:p Smith had trouble understanding some of the medical explanations. <o:p</o:p But he knew two things. First, he was looking at the only person he knew trying to find a cure for his daughter's disease. Second, the man needed money.<o:p</o:p "How much will it take?" he asked. Gatti estimated $300,000 a year, minimum, to keep his lab running. Smith was wealthy, but not that wealthy. He made a promise. He would put up at least $100,000 of his own money, every year, and raise the rest through a foundation he would form immediately. <o:p</o:p Gatti left lunch convinced he had met the Medici who would finance his work. <o:p</o:p Smith left wondering how he would raise the cash. Having spent a lifetime solving other people's money problems, he had never needed other people's financial help. Suddenly he had to learn to ask for it. So he dove in. Whenever an opportunity presented itself, he talked about Becca and other kids with A-T, and asked for money. He turned to developers, bankers, real estate moguls and others. "I wrote this very emotional letter," he recalls. Friends and business associates who received it helped him keep Gatti going for another year. <o:p</o:p There was also his neighbor, recording mogul Jerry Moss, who decided to renovate his house in Bel-Air, where the Smiths lived at the time. "He had this construction project going for a long time, and there was a big pile of earth sitting there uncovered," Smith says. "Every time the wind blew, the dust covered our house. Pretty soon we had spores growing on our roof, and that can cause all kinds of health problems. I called him, and he set up a breakfast at the Hotel Bel-Air for us to meet and talk." <o:p</o:p Smith went not knowing what to expect. He found an amiable man who wanted to be a good neighbor. When Moss asked what he could do, Smith told him: cover the excavated earth, delay the start of each workday until 8 a.m. and write a $10,000 check for the A-T Medical Research Foundation. Moss did it all, and continued sending checks on a regular basis. That kind of largess was repeated again and again by the wealthy people Smith knew. <o:p</o:p But as successful as he was raising money one check at a time, he knew that the foundation would not thrive on personal arm-twisting. Pam Smith began organizing parties. In 1986 she held a women's luncheon at the Regency Club that yielded about $30,000 for the lab. For more than a decade, the annual luncheon and small parties kept the research going. Still, Smith kept looking for a way to increase the cash flow. In 1996 an associate in Smith's office suggested an annual luncheon for the region's real estate industry, during which the audience could listen to a big-name speaker and make donations. The response was so strong that Smith moved the event to a bigger banquet hall to meet the demand for $150 seats. Since then, the George Smith Partners Luncheon has become the largest real estate industry gathering in California, drawing 1,500 people and generating $300,000 a year for the foundation. Last year's speaker was businessman Jerry Reinsdorf, owner of the Chicago Bulls. <o:p</o:p *****************************************************************************<o:p</o:p With the Smiths taking care of the money, Gatti's research team grew, acquired expensive equipment and moved into a new laboratory at UCLA. The Smiths funded two small conferences to bring together the dozen or so experts in the field. In 1987, Dr. Swift in North Carolina supported Gatti's thesis that A-T and cancer are linked. In the New England Journal of Medicine, Swift wrote that women with a defective A-T gene are five times more likely to develop breast cancer. <o:p</o:p Not long after, Gatti called Smith and told him to come to the lab right away. Smith arrived as a noisy computer printer was screeching out a massive document. The data proved that Gatti had tracked the A-T gene to a region on chromosome 11. "It's like we were looking all over the world for a certain location and had narrowed it to Southern California," Gatti told Smith. "We were getting much closer." His task no longer seemed Herculean. The U.S. Department of Energy, which was interested in the effect radiation has on A-T carriers, granted funds to accelerate the research, freeing some cash from Smith's foundation. So Gatti suggested that Smith look up a scientist at the University of Tel Aviv in Israel. <o:p</o:p The Israeli was Yosef Shiloh, and he had been drawn to A-T through patients he first discovered in the Palestinian community in the 1970s. Hidden away by their families, the children displayed so many different symptoms that Shiloh was baffled and moved by their plight. <o:p</o:p He wanted to help. Shiloh's commitment was obvious to Smith, who invested in his work and, in effect, helped create a competitor for Gatti. Gatti's success also led to a groundswell of research elsewhere. Soon scientists in Seattle, Canada, Holland and England were in the hunt. All agreed to share information that would speed the search for the exact spot on the chromosome where the A-T gene lived. <o:p</o:p By 1994, about 10 researchers were focused on chromosome 11 in the search for the gene. In calls from laboratory to laboratory, the gene hunters traded reports on the territory they had covered, and excluded. Gatti reveled in the progress, certain that at any moment the prey would be cornered. <o:p</o:p Suddenly all the talking stopped. A basic human impulse had set in. As they moved tantalizingly closer to their target, the scientists began to realize that one of them would get there first. Someone would be credited with a breakthrough. Trust suffered. "At some point Yosef heard something that made him think we had found it, but that we weren't telling him," Gatti says. "That wasn't true. But all of a sudden no one was sharing anything. I knew we had narrowed it down pretty far, and I knew that someone would get there within a few weeks." <o:p</o:p Smith could hear Gatti's anxiety as he explained that the other researchers had fallen silent. He felt a deep affection for his old friend, the man who had been his first and only hope at the beginning. But in this race, Smith was merely a spectator. He didn't tell Gatti that days before Shiloh had called to say it was almost over. "I'm going to get there, George," Shiloh had said. "And I'm going to get there first." <o:p</o:p Like a Formula One driver using the draft of a car ahead to slingshot over the finish line, Shiloh used every bit of knowledge accumulated by the researchers to win the race to isolate the A-T gene in 1995. Newspapers and TV broadcasts around the world announced the discovery as a major advance in cancer research even if, sadly, it was not the answer to curing A-T. Shiloh got his picture in Science magazine. Gatti had the equivalent of honorable mention. <o:p</o:p But the sting of second place didn't last long. Gatti and teams around the world zeroed in on the gene and began taking it apart. Their findings, detailed in scores of medical journal reports, make clear that a normal A-T gene transmits signals that tell many kinds of cells when and how to grow and function, and how to repair themselves when damaged. This is how the body normally prevents cancers from developing after DNA has been damaged. What also is clear is that people who carry one copy of the mutant A-T gene, handed down by their mother or father, are more susceptible to cancer. People who get the mutation from both parents are far more vulnerable. They are true A-T patients. <o:p</o:p More than 100 laboratories worldwide are now looking into the once-orphaned disease. Mice that bear the mutant gene have been developed to aid experiments. And last February, a world conference on A-T drew hundreds of scientists, and presentations revealed new information on everything from the A-T gene's influence on brain development to its effect on the risk of breast cancer. <o:p</o:p The most promising research is aimed at finding ways to boost the A-T gene's cancer-fighting mechanisms, Gatti says. Since it would stimulate natural, tumor-fighting responses, this kind of treatment would be especially effective in attacking late-stage cancers that have metastasized throughout the body. <o:p</o:p The elusive cure for A-T most likely lies in work being done on so-called "neural stem cells," which produce many types of brain and nerve cells. Already being tested in patients with Parkinson's disease, stem cell transplants may one day be used to help A-T patients grow new cells with properly working A-T genes. Gatti is pursuing this idea in collaboration with Jean DeVellis and other established stem cell researchers at UCLA. Once again, the Smiths will provide the seed money for the effort. <o:p</o:p ***************************************************************************** <o:p</o:p Scientists immersed in laboratory work can feel removed from the suffering caused by the microscopic mutant they chase like a target in some video game. That is not the case among A-T researchers. They know Becca Smith too well. At the February conference, before any of the science was discussed, doctors and investigators sang happy birthday and presented her a heart-shaped cake. She had turned 21, no small achievement for someone with A-T, but, of course, they were celebrating something bigger. <o:p</o:p For nearly two decades, Becca has allowed herself to be the young face of a terrible illness. Her mother and, most of all, her father financed the search for a cure when no one else would, or could. They contributed more to science and medicine than many highly trained experts do in a lifetime. <o:p</o:p "If it wasn't Becca who got A-T, and if George hadn't been her father, we wouldn't have been there at all," Gatti says. <o:p</o:p Yet for all the advances made in cancer research, everyone who stood to honor Becca knew that a treatment or cure that would save her life has not yet been found. And no one knows if that will happen in time. But the Smiths' investment in research, like the down payment on a good piece of real estate, has leverage. It has produced a breakthrough in basic science that will benefit all of humanity. And it has yielded a dividend of hope where none existed before.