HARVEY Pass, the chief of thoracic surgery at the National Cancer Institute, in Bethesda, Maryland, was sitting in his laboratory one spring afternoon in 1993 when Michele Carbone, a wiry young Italian pathologist who was working as a researcher at the NCI, strode in with an unusual request. Pass had never before met Carbone, and had talked to him for the first time, on the telephone, only a few hours before. Now Carbone was asking Pass for his help in proving a controversial theory he had developed about the origins of mesothelioma, a deadly cancer that afflicts the mesothelial cells in the lining of the chest and the lung. Mesothelioma was virtually unheard of prior to 1950, but the incidence of the disease has risen steadily since then. Though it is considered rare -- accounting for the deaths of about 3,000 Americans a year, or about one half of one percent of all domestic cancer deaths -- the disease is particularly pernicious. Most patients die within eighteen months of diagnosis.
Pass, one of the world's leading mesothelioma surgeons, knew, like other scientists, that the disease was caused by asbestos exposure. But Carbone had a hunch he wanted to explore. He told Pass that he wondered if the cancer might also be caused by a virus -- a monkey virus, known as simian virus 40, or SV40, that had widely contaminated early doses of the polio vaccine, but that had long been presumed to be harmless to people.
Pass listened as Carbone described for him the history of the early polio vaccine. A breakthrough in the war against polio had come in the early 1950s, when Jonas Salk took advantage of a new discovery: monkey kidneys could be used to culture the abundant quantities of polio virus necessary to mass-produce a vaccine. But there were problems with the monkey kidneys. In 1960 Bernice Eddy, a government researcher, discovered that when she injected hamsters with the kidney mixture on which the vaccine was cultured, they developed tumors. Eddy's superiors tried to keep the discovery quiet, but Eddy presented her data at a cancer conference in New York. She was eventually demoted, and lost her laboratory. The cancer-causing virus was soon isolated by other scientists and dubbed SV40, because it was the fortieth simian virus discovered. Alarm spread through the scientific community as researchers realized that nearly every dose of the vaccine had been contaminated. In 1961 federal health officials ordered vaccine manufacturers to screen for the virus and eliminate it from the vaccine. Worried about creating a panic, they kept the discovery of SV40 under wraps and never recalled existing stocks. For two more years millions of additional people were needlessly exposed -- bringing the total to 98 million Americans from 1955 to 1963. But after a flurry of quick studies, health officials decided that the virus, thankfully, did not cause cancer in human beings.
After that the story of SV40 ceased to be anything more than a medical curiosity. Even though the virus became a widely used cancer-research tool, because it caused a variety of tumors so easily in laboratory animals, for the better part of four decades there was virtually no research on what SV40 might do to people.
Carbone had reviewed some old research papers on the contamination and some of the early tests on SV40. He had even reviewed the notes from a crucial 1963 epidemiological study, by Joseph Fraumeni, an NCI researcher, which had concluded that children inoculated with contaminated vaccine did not show increased mortality rates. The studies did not impress Carbone: no one had systematically searched for evidence of the virus in tumors, and, as Fraumeni himself noted, the epidemiological study was too short to have detected certain slow-developing cancers. (Mesothelioma can take twenty to forty years to develop.)
Carbone had just finished a series of experiments in which he had injected the virus into dozens of hamsters. Every one of them developed mesothelioma and died within three to seven months. The results made Carbone wonder if SV40 might also play a role in human mesothelioma. He had come to see Pass because he had heard that the senior surgeon had meticulously saved tumor tissue from every one of the dozens of mesothelioma surgeries he had performed, and now had one of the largest collections of mesothelioma biopsies in the world. Carbone asked Pass if he could look for SV40 DNA in Pass's tumor-tissue samples, using a sophisticated molecular technique, known as polymerase chain reaction, or PCR, to extract tiny fragments of DNA from the frozen tissue and then amplify and characterize them.
As they talked, Pass became more and more impressed with Carbone. The young scientist was energetic and extremely self-confident -- something Pass attributed to Carbone's surgical patrimony. (Carbone's father is a well-known orthopedic surgeon in Italy.) When Carbone had finished describing his proposed experiment, Pass realized that the implications were potentially significant. Only a handful of viruses have been directly associated with human cancers, and none of them are simian in origin. If SV40 was linked to mesothelioma in people, might it also cause bone and brain cancers in human beings, as it had done in hamsters? What if the monkey virus could spread from person to person? And if the virus was cancer-causing, or oncogenic, what was one to make of the fact that millions of Americans had been exposed to it as part of a government-sponsored vaccination program?
"I thought to myself, He's got this wild-assed idea," Pass recalls. "If it's true, it's unbelievable. Even if it's not, I'm going to get a hell of an education in state-of-the-art molecular biology."