FINALLY, THE SMOKING GUN. Molecular biologist Eric Moon-shong Tang, of the University of Texas M. D. Anderson Cancer Center, knew it was there. So did most other scientists, doctors, and citizens. Now, in a year in which the dishonesty of Big Tobacco became absurdly conspicuous, Tang and a team of scientists found what many have sought for years: irrefutable proof that smoking causes lung cancer.
Evidence of the relationship between tobacco smoke and lung cancer has always been copious but circumstantial; despite countless statistical studies that pointed the finger at tobacco, there had never been a proven link. And given the host of environmental cancer pathogens breathed by people every day, the tobacco companies and their political defenders always had an out. “They could always say, How can we be sure?’” says the 54-year-old Tang, who lives in Bastrop and works at the Anderson Center Science Park near Smithville, southeast of Austin. “It was always like a case where a smart lawyer could say, Maybe another guy did it.’ Now there is no doubt. Elements in tobacco smoke cause damage to lung tissue at the genetic level, which causes cancer.”
Tang was born and raised in Mialo, Taiwan, the youngest son among eight children. Following Chinese custom, his older siblings went into the family business; Tang was groomed for higher education and a life beyond the island. After earning an under-graduate degree in biology in Taiwan, Tang immigrated to the U.S. in 1972, with his wife, Ya-ing, and two children, son Yen-len and daughter Yen-yee. He received his Ph.D. in molecular biology from the University of Texas at Dallas, then did postdoctoral work at Stanford University and Washington University in St. Louis. He joined the M. D. Anderson staff in 1982.
The hard science that led Tang and his team codirector, Gerd Pfeifer of the Beckman Research Institute in Duarte, California, to their breakthrough discovery sounds exotic but is, in fact, remarkably simple. Scientists have known for some time that 50 percent of all cancer and 70 percent of all lung cancer involve damage to a gene known as P53. This gene serves as a tumor suppressor in the body’s genetic system, a kind of traffic cop that slows or halts altogether the inappropriately rapid cell replication that occurs in tumors.
Scientists have also long known that tobacco smoke contains a powerful carcinogen called benzo(a)pyrene (BAP), which, when metabolized by the body, produces a highly mutagenic substance called benzo(a)pyrene diol epoxide (BPDE). BPDE tends to produce certain signature mutations in the P53 geneprecisely the sort of mutations, it turns out, that are common in lung tumors.
Tang, who had been fascinated with the mechanics of DNA damage and repair for years, reduced this web of circumstantial evidence to hard proof. By introducing BAP to human lung cells and then observing the cells’ response through a new gene-mapping technique, Tang, Pfeifer, and their colleagues were actually able to see the deadly dynamics of lung cancer at the most elementary level of human life, the DNA. The BPDE, they discovered, quickly bound chemically to the P53 gene, compromising its vital regulatory function. Tang was able to ascertain precisely where on the gene the plunder took place by “cutting,” or marking, the DNA with purified enzymes. He discovered that the BPDE zeroed in on three “mutational hotspots” especially vulnerable links in the DNA chain. “There it is,” says Tang proudly, pointing to a series of DNA x-rays of the sort made famous in the O. J. Simpson trial. “Where you see the dark marks is where the chemical has damaged the gene. It really is that simple.”
For Tang, the P53-BAP linkage was the culmination of three years of diligent, often tedious work. “It just wasn’t possible until we had the new imaging techniques,” he says. “Now we can see down at the level where a disease like this works.”
The legal and political implications of Tang’s findings are huge, providing private and public anti-tobacco forces yet another cudgel to whack the industry with. Not surprisingly, the tobacco industry seemed unconvinced by the evidence. Following the publication of Tang’s research in the October 18, 1996, issue of the magazine Science, tobacco giant Brown and Williamson released a statement asserting that BAP is a common environmental substance that can invade the body from many different sources.
Meanwhile, Tang seems less concerned with his work’s short-term impact on the tobacco wars than with its long-term ramifications in labs and clinics. With the mechanics of lung cancer at the genetic level finally laid bare, is a cure for the nation’s leading cause of cancer death within reach? What of the other cancers now linked to P53 damage? Can a damaged P53 gene be replaced by a healthy one via gene therapy? What is it about the P53 gene of some individuals that seems to make them impervious to cancer?
Tang will try to answer these questions in the future. In the meantime, he seems proudest of the fact that the discipline of molecular biology, once considered so esoteric as to be irrelevant to the layman, has provided the public with “something tangible that they can see. It’s like finally finding the suspect’s fingerprint at the scene of the crime. Everybody can understand that.”
