www.gulfwarvets.com/virus.htm


      Return to this issue's Table of Contents. F E B R U A R Y  2 0 0 0 

      A simian virus known as SV40 has been associated with a number of rare 
      human cancers. This same virus contaminated the polio vaccine administered 
      to 98 million Americans from 1955 to 1963. Federal health officials see 
      little reason for concern. A growing cadre of medical researchers disagree 

      by Debbie Bookchin and Jim Schumacher
      (The online version of this article appears in three parts. Click here to 
      go to part two or part three.)
      ARVEY 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. 
      Discuss this article in Post & Riposte. 
      More on politics & society in The Atlantic Monthly and Atlantic Unbound.

      See a collection of Atlantic articles on health care. 
      From the archives: 
      "The Clinical Trials Bottleneck," by Francine Russo (May, 1999)
      Randomized clinical trials are the most conclusive way to test new 
      treatments for cancer, but these trials are often resisted by patients, by 
      doctors, and by insurers reluctant to pay for unproven therapies. 
      "A New Germ Theory," by Judith Hooper (February, 1999)
      The dictates of evolution virtually demand that the causes of some of 
      humanity's chronic and most baffling "noninfectious" illnesses will turn 
      out to be pathogens -- that is the radical view of a prominent 
      evolutionary biologist. 
      "Could Mad-Cow Disease Happen Here?", by Ellen Ruppel Shell (September, 
      1998)
      One would think, given the deadly outbreak in Britain, that the U.S. 
      government would by now have taken every possible precaution. Not so. 
      "Good News and Bad News about Breast Cancer," by David Plotkin, M.D. 
      (June, 1996)
      Women are more alarmed than they need to be about the chances that they 
      will develop breast cancer. But they are also more confident than they 
      should be that the advances medicine has made in treating the disease and 
      prolonging life mean that it can be cured. 
      Related links: 
      "The Lethal Dangers of the Billion-Dollar Vaccine Business," by Andrea 
      Rock (December, 1996)
      "With government approval, drug companies sell vaccines that can leave 
      your child brain damaged, can spread polio from your baby to you -- and 
      can even kill. Safer stuff is available. Here's why you haven't been 
      getting it." (A health report in Money Magazine.) 
      "SV-40 Contamination of Poliovirus Vaccine," by Dr. John Martin (July, 
      1997)
      An article by a doctor at the Center for Complex Infectious Diseases in 
      Rosemead, California. 
      National Vaccine Information Center
      "The National Vaccine Information Center is a national, non-profit 
      educational organization founded in 1982. It is ... dedicated to the 
      prevention of vaccine injuries and deaths through public education." 
      The Vaccine Page
      "The Vaccine Page provides access to up-to-the-minute news about vaccines 
      and an annotated database of vaccine resources on the Internet." 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. 

            One of SV40's constituent  
            proteins, large T-antigen: "the most  
            oncogenic protein ever discovered"    


      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." 
      Others at the National Institutes of Health -- including some of the 
      scientists who had been around at the time of the contamination scare -- 
      were less receptive to the novel theory. They told Carbone that the last 
      thing anyone wanted to hear was that the exalted polio vaccine was linked 
      to cancer. Too much was at stake. Implicating a vaccine contaminant in 
      cancer -- even if the contamination occurred some forty years ago -- might 
      easily shake public confidence in vaccines in general. And besides, 
      everyone knew that asbestos was the cause of mesothelioma. 
      Carbone sought the advice of two renowned pathologists, Umberto Saffiotti, 
      the chief of the NCI's Laboratory of Experimental Pathology, and Harold L. 
      Stewart, a former director of pathology at the NCI who was once the head 
      of the American Association for Cancer Research. Both urged Carbone to 
      follow his intuition. "Forget what people tell you," Stewart told Carbone. 
      "They told me I was wrong all my life. If you want to do it, you should, 
      or you will regret it." That spring afternoon in 1993, with Pass's 
      mesothelioma samples in hand, Carbone called an old friend, Antonio 
      Procopio, a professor of experimental pathology in Italy who had worked 
      for three years at the NIH. "I asked him if he was willing to do this 
      crazy project with me," Carbone says. "I told him I could not pay him or 
      his expenses." A month later Procopio arrived in Bethesda. "We had no 
      money," Carbone recalls. "He slept in my house for six months, and we 
      worked day and night." 
      It turned out that Pass's samples were loaded with the monkey virus: 60 
      percent of the mesothelioma samples contained SV40 DNA; the nontumor 
      tissues used as controls were negative. Moreover, Carbone found that in 
      most of the positive samples he tested, the monkey virus was active, 
      producing proteins -- suggesting to Carbone that the SV40 was not just an 
      opportunistic "passenger virus" that had found a convenient hiding place 
      in the malignant cells but was likely to have been involved in causing the 
      cancer. 
      In 1994 Carbone, Pass, and Procopio published the results of their 
      experiment in Oncogene, one of the world's leading cancer-research 
      journals. They proposed SV40 as a possible co-carcinogen in human 
      mesothelioma. It was the first time researchers had put forward hard 
      evidence that the all-but-forgotten vaccine contaminant might cause cancer 
      in human beings. 
      A Solution to an Enigma
      ICHELE Carbone is almost stereotypically Italian: generous with his 
      emotions, outspoken, and jovial. He is strikingly handsome, with large 
      brown eyes and shoulder-length brown hair. Carbone grew up in a cultured 
      home in Calabria, on the shores of the Mediterranean in southern Italy. As 
      a youth he often spent hours poring over medical texts, some of them 300 
      years old, in the voluminous library started by the first of the seven 
      generations of Carbone physicians to date. If his father gave him science, 
      from his mother he may have inherited the strong intuition that is his 
      distinguishing characteristic as a researcher. She is an accomplished 
      artist whose work is exhibited widely in Europe. 
      Carbone graduated in 1984, at the top of his class, from the University of 
      Rome Medical School, one of the largest in the world, and quickly won a 
      coveted NIH doctoral fellowship. In 1993 he received a Ph.D. in human 
      pathology. In less than a decade he has risen to the top of his 
      profession. Today he is internationally recognized as an expert in 
      mesothelioma. 
      Since 1994 Carbone has written more than twenty studies and reviews 
      investigating SV40's link to human cancer. "There is no doubt that SV40 is 
      a human carcinogen," he says. "SV40 is definitely something you don't want 
      in your body." Carbone suggests that the virus works in tandem with 
      asbestos or by itself to transform healthy mesothelial cells into 
      cancerous ones. 
      Since he published his first study, scientists at seventeen major 
      laboratories -- in the United States, Great Britain, France, Belgium, 
      Italy, and New Zealand -- have confirmed Carbone's research with respect 
      to the presence of SV40 in human mesothelioma. Their results point to a 
      solution to an enigma that long puzzled researchers. At least 20 percent 
      of mesothelioma victims report no asbestos exposure, and only 10 percent 
      of people who have had heavy exposure to asbestos ever develop 
      mesothelioma. The experiments suggest that SV40 may be another factor at 
      work in the tumors. 
      Two very recent studies, from Finland and Turkey, found no SV40 in 
      domestic mesothelioma samples but did find it, respectively, in American 
      and Italian samples. The authors observe that their negative findings lend 
      support to the theory that contaminated polio vaccine is associated with 
      the disease: neither Turkey nor Finland used SV40-contaminated vaccines. 
      Today Finland has one of the lowest rates of mesothelioma in the Western 
      world. 
      The virus has also been located in other kinds of tumors. More than a 
      dozen laboratories have found SV40 in various kinds of rare brain and bone 
      tumors. In 1996 Carbone reported that he had found SV40 in a third of the 
      osteosarcomas (bone cancers of a type that afflicts about 900 Americans a 
      year) and nearly half of the other bone tumors he tested -- research that 
      has since been confirmed by numerous laboratories. The virus has also been 
      detected in pituitary and thyroid tumors. 
      The possibility of a link between SV40 and brain tumors is particularly 
      intriguing. Like mesothelioma, brain tumors have become dramatically more 
      common in recent years. Brain tumors will be diagnosed in about 3,000 
      children in the United States alone this year. In 1995 Janet Butel, the 
      chairman of the department of molecular virology and microbiology at the 
      Baylor College of Medicine, in Texas, and her chief collaborator, John 
      Lednicky, also a Baylor virologist, reported that they had found SV40 in a 
      number of children's brain tumors. Butel and Lednicky reported that DNA 
      sequencing revealed that the virus was not a hybrid but rather authentic 
      SV40 -- the same as the SV40 found in monkeys. In the fall of 1996 an 
      Italian research team, led by Mauro Tognon, of the University of Ferrara, 
      announced that it had found SV40 DNA in a large percentage of brain and 
      neurological tumors, including glioblastomas, astrocytomas, ependymomas, 
      and papillomas of the choroid plexus. The researchers suggested that SV40 
      may be a "viral cofactor" involved in the sharp rise in human brain 
      tumors. Late last year an extensive study undertaken in China reinforced 
      those results. The study examined sixty-five brain tumors, finding SV40 in 
      each of the eight ependymomas and two choroid-plexus papillomas, common 
      brain tumors among children. It also found the virus in 33 to 90 percent 
      of five other kinds of brain tumor examined. The authors, writing in the 
      November, 1999, issue of Cancer, noted that the virus was actively 
      expressing proteins. 
      Recent research also indicates that SV40 has gained a secure foothold in 
      the human species. In 1996 Tognon and his collaborators reported that they 
      had also found the virus in 45 percent of the sperm samples and 23 percent 
      of the blood samples they tested from healthy people, suggesting that the 
      monkey virus could spread through sexua| contact or unscreened blood 
      products. In 1998 the presence of SV40 antibodies in human blood samples 
      was reported by Butel, who tested several hundred American blood samples 
      and found antibodies to SV40 in about 10 percent of them. Butel's 
      laboratory also tested samples from children born from 1980 to 1995 -- 
      decades after the contaminated vaccine was removed from the market. A 
      surprising six percent tested positive -- offering evidence that the virus 
      may now be spreading from person to person, including from mother to 
      child. 
      Continued... 
      (The online version of this article appears in three parts. Click here to 
      go to part two or part three.)


      Debbie Bookchin specializes in health and political issues. Her articles 
      have appeared in The New York Times, The Boston Globe, and The Nation. Jim 
      Schumacher is a freelance writer who lives in Vermont. His articles have 
      appeared in Boston magazine, The Boston Globe, and Newsday.


      Illustrations by Giacomo Marchesi.
      Copyright © 2000 by The Atlantic Monthly Company. All rights reserved.
      The Atlantic Monthly; February 2000; The Virus and the Vaccine - 00.02; 
      Volume 285, No. 2; page 68-80.