HEALTH • Jack Roth
He’s helping solve one of medicine’s biggest mysteries: cancer. It’s all in the genes.
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In the early nineties molecular biologists began using viruses to perform gene therapy. Working with scientists at Introgen Therapeutics, an Austin biotech company he had co-founded, Roth developed a technique to replace the defective p53 gene, using the common cold virus as a vehicle to carry a healthy version of the gene into the malfunctioning cell. At M. D. Anderson, Roth then successfully replaced defective p53 in animals. “This not only corrected the p53 defect but it also caused the cancer cells to self-destruct,” he recounts. “I was astonished to see that. Cancer cells have all these different genetic deletions and defects, and here we were correcting just one and having this profound effect.” When he proposed trying the concept in people, however, he ignited a raging controversy: Health experts still feared that the viruses used to ferry the genes could inadvertently wreak havoc, and cancer specialists were skeptical that fixing one gene would stop a systemic disease.
After more than a year, Roth finally won the right to proceed. In 1994 he made medical history by inserting a long hypodermic needle into the chest of a furnituremaker. Roth had established that a tumor in the man’s lungs contained defective p53. Depressing the plunger of the needle, he injected the growth with a genetically altered virus. Ordinary viruses invade a cell and usurp its machinery, turning the cell into a factory that churns out more virus; Roth’s altered virus wormed its way into the nucleus of the cancer cells and reinstated a working copy of p53. After several injections, the man’s tumor started to shrink. “Here he was, the first patient we were treating, and it looked like the treatment was working,” says Roth.
The treatment may have worked locally, but it didn’t save the life of the furnituremaker. He died four months later from tumors that demolished his kidneys. (Because of federal restrictions governing the experiment, Roth was not allowed to treat other parts of the man’s body with gene therapy.) Eight other patients enrolled in that first experiment, and every one of them died—they were so sick that their fate was not a surprise. Still, the trial was considered a success: It proved that gene therapy was safe and that p53 was being successfully inserted into cancer cells.
In Roth’s next experiment, several patients, who also had terminal cancer, experienced seemingly miraculous turnarounds. One was 73-year-old Verna Clouse, whom I met during a checkup last year. Clouse has silver-blond hair, blue eyes, and a personality like a bear hug. In the examining room she whipped off her aqua-green track suit without a qualm. “I have five sisters,” she announced, “and I’m so old it doesn’t matter.” I smiled, imagining how she got along with the reserved Dr. Roth.
Four years earlier, a routine CAT scan had revealed a spot on Clouse’s lung. She had smoked for 52 years and was already wheezing from emphysema; radiation and chemotherapy had only slowed the cancer down. It seemed certain she would die—a doctor told her, “You know, there’s no cure for cancer.” One day Clouse was watching TV when she saw a brainy-looking guy talking about p53. It was Roth. Clouse enrolled in his clinical trial of the gene therapy’s effect on lung cancer. By her second visit to M. D. Anderson, her tumor was shrinking. Every month afterward, it shrank more.
“Here’s our star patient!” Roth called heartily as he entered the room. “Your x-rays look great! You still have that little abnormality, but it’s even less now. I think it’s probably just a scar from the radiation.”
Later I asked Roth if Clouse had been cured. “Well, we don’t use that word,” he said. “She certainly has done very well.” p53 is not a cure per se—it does not rid the body of cancer. Rather, when used in combination with radiation, chemotherapy, and surgery, it greatly enhances a doctor’s ability to control life-threatening tumors, at least for a while. Unfortunately, after more than a year’s reprieve, Clouse’s cancer recently metastasized and showed up in her lymph glands. She is fighting it just as gamely as she fought her lung cancer, but her prognosis is once again bleak.
Roth is soldiering on too. After the p53 therapy showed such promise with lung cancer, Introgen quickly applied for permission from the Food and Drug Administration to use it against other forms of the disease. In June Introgen announced that the results of a clinical trial involving head and neck cancers had been so compelling that the company was asking the FDA to put the p53 therapy on the fast track for approval. (The treatment successfully shrank some tumors by more than 50 percent and stopped the growth of others entirely, without any serious side effects; twice as many patients survived as Roth had expected.) If the FDA grants the request, Introgen is likely to become the first biotech company in the country to receive federal approval to market a gene therapy for cancer.
Altogether it has been a year of astounding developments in the field: Deaths from cancer started dropping for the first time ever, the incidence of new cases has been falling, and reports of another new, highly successful approach, involving anti-angiogenesis drugs (which cut off the blood supply to tumors), caused a flurry of excitement. Cancer comes in so many permutations that no single treatment is likely to prove a cure-all, but these emerging therapies clearly mark a watershed moment. All of a sudden experts are predicting that cancer may soon be a disease people can live with, like diabetes or AIDS. For years Jack Roth and the white-coated doctors at M. D. Anderson have fought a losing battle. Now, despite their inculcation against the blurring effects of sentiment and their allegiance to cold facts, many are beginning to believe they may actually defeat the most tenacious disease afflicting the human race.
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