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by William Carlsen

NOTE: Please feel free to email this San Francisco Chronicle Reporter and congratulate him on this terrific piece of investigative journalism.

A growing number of medical researchers fear that a monkey virus that contaminated polio vaccine given to tens of millions of Americans in the 1950s and '60s may be causing rare human cancers.

For four decades, government officials have insisted that there is no evidence the simian virus called SV40 is harmful to humans. But in recent years, dozens of scientific studies have found the virus in a steadily increasing number of rare brain, bone and lung-related tumors - the same malignant cancer SV40 causes in lab animals.

Even more troubling, the virus has been detected in tumors removed from people never inoculated with the contaminated vaccine, leading some to worry that those infected by the vaccine might be spreading SV40.

The discovery of SV40 in human tumors has generated intense debate within the scientific community, pitting a handful of government health officials, who believe that the virus is harmless, against researchers from Boston to China who now suspect SV40 may be a human carcinogen. At stake are millions of research dollars and potential medical treatments for those afflicted with the cancers SV40 may be causing.

In April, more than 60 scientists met in Chicago to discuss the controversial virus and how it works to defeat certain cells' natural defenses against cancer.

"I believe that SV40 is carcinogenic (in humans)," said Dr. Michele Carbone of Loyola University Medical Center in Maywood, Ill. "We need to be creating therapies for people who have these cancers, and now we may be able to because we have a target - SV40."

But scientists at the National Cancer Institute say their studies show almost no SV40 in human tumors and no cancer increase in people who received the contaminated vaccine.

"No one would dispute there's been a widespread, very scary exposure to the population of potentially cancer-causing virus," said Dr. Howard Strickler, NCI's chief investigator. "But none of our studies and other major analyses have shown an inkling of an effect on the population."

Critics charge, however, that the few studies done by the government are scientifically flawed and that health officials have downplayed the potential risks posed by SV40 ever since they learned in 1961 that the virus contaminated the polio vaccine and caused tumors in rodents.

"How long can the government ignore this?" asked Dr. Adi Gazdar, a University of Texas Southwestern Medical Center cancer researcher. "The government has not sponsored any real research. Here's something possibly affecting millions of Americans, and they're indifferent.

"Maybe they don't want to find out."

The recent SV40 discoveries come at a time of growing concern over the dangers posed by a range of animal viruses that have crossed the species barrier to humans, including HIV, which scientists now believe came from chimpanzees and ultimately caused the AIDS epidemic.

Based on dozens of interviews and a review of the medical research, this is the story of how the campaign to eradicate polio may have inadvertently permitted another potentially deadly monkey virus to infect millions of people - and why the government for years discounted the accumulating evidence suggesting that SV40 may be a health risk for humans.

Polio Epidemic, 1955

During the first half of the 20th century, polio struck down hundreds of thousands of people, leaving many paralyzed - some in iron lung machines - and killing others. The worst year was 1952, when more than 57,000 polio cases were reported in the United States. Three thousand died.

Then on April 12, 1955, Dr. Jonas Salk, a slightly built, soft-spoken researcher from Pittsburgh, mounted the podium at the University of Michigan and announced that he had developed a vaccine. That afternoon, the government licensed the vaccine for distribution.

Salk's vaccine was made by growing live polio virus on kidney tissue from Asian rhesus monkeys. The virus was then killed with formaldehyde. When the vaccine was injected in humans, the dead virus generated antibodies capable of fending off live polio.

Dr. Dwight Murray, then chairman of the American Medical Association, called Salk's announcement "one of the greatest events in the history of medicine."

Within weeks, the stockpiled vaccine was being injected into the arms of millions of people worldwide.

Virus and the Tumors, 1959

Four years later, Bernice Eddy, a researcher at the National Institutes of Health, noticed something strange while looking through her microscope. Monkey kidney cells - the same kind used to make the vaccine - were dying without apparent cause.

So she tried an experiment. She prepared kidney extracts from eight to 10 rhesus monkeys and injected tiny amounts under the skin of 23 newborn hamsters. Within nine months, "large, malignant, subcutaneous tumors" appeared on 20 of the animals.

On July 6, 1960, concerned that a monkey virus might be contaminating the polio vaccine, Eddy took her findings to Dr. Joseph Smadel, chief of the NIH's biologics division. Smadel dismissed the tumors as harmless "lumps."

The same year, however, at a Merck laboratory in Pennsylvania, Dr. Maurice Hilleman and Dr. Ben Sweet isolated the virus. They called it simian virus 40, or SV40, because it was the 40th virus found in rhesus kidney tissue.

Immunization Campaign, 1961

By then, the nation was winning the war against polio. Nearly 98 million Americans - more than 60 percent of the population - had received at least one injection of the Salk vaccine, and the number of cases was plummeting.

At the same time, an oral polio vaccine developed by virologist Albert Sabin was in final trials in Russia and Eastern Europe, where tens of millions had been inoculated, and it was about to be licensed in the United States. Unlike the Salk vaccine, the oral version contained a live but weakened form of polio virus and promised lifelong immunity.

But U.S. Public Health Service officials were worried. Tests had found SV40 in both the Sabin and Salk vaccines - it was later estimated that as much as a third of the Salk vaccine was tainted - and that SV40 was causing cancer in lab animals.

In early 1961, they quietly met with the agency's top vaccine advisers. The agency found no evidence that the virus had been harmful to humans, but in March, the officials ordered manufacturers to eliminate SV40 from all future vaccine.

New procedures were adopted to neutralize the tainted polio virus seed stock and SV40-free African green monkeys were used to produce the bulk vaccine instead of rhesus monkeys.

But officials did not recall contaminated Salk vaccine - more than a year's supply - still in the hands of the nation's doctors.

And they did not notify the public of the contamination and SV40's carcinogenic effect on newborn hamsters.

Hilleman would later explain that government officials were worried that any potentially negative information could ignite a panic and jeopardize the vaccination campaign.

The first public disclosure that the Salk vaccine was contaminated came in the New York Times on July 26, 1961. A story on Page 33 reported that Merck and other manufacturers had halted production until they could get a "monkey virus" out of the vaccine.

When asked to comment, the U.S. Public Health Service stressed there was no evidence the virus was dangerous.

No Cause For Alarm, 1962

The next year, a young Harvard-trained epidemiologist named Dr. Joseph Fraumeni joined the National Cancer Institute and was assigned one of the agency's most important projects: to determine if there was any cancer increase among those injected with the Salk vaccine.

His research would form the basis of the government's position for decades.

Working with two colleagues, Fraumeni tested stored vaccine samples from May and June of 1955, the first months of the national immunization campaign, then ranked the samples according to how much SV40 they contained - no, low or high amounts.

It would be the only time U.S. health officials measured the level of SV40 in the 1955-1962 vaccine. Stored samples from that period were later discarded.

Fraumeni identified the states where the SV40-contaminated vaccines had been distributed during those two months. California, for example, received vaccine with a low level of the virus.

The study looked at cancer mortality rates for 6- to 8-year-old children vaccinated during that narrow time frame, tracking the group for four years.

The findings, which were published in the Journal of the American Medical Association, showed no significant difference in cancer deaths in states with high or low levels of SV40 in the vaccine when compared with cancer deaths in states with no SV40 in the vaccine.

Cleveland Children, 1976

Fourteen years later, after isolated reports linking the virus and human cancers, Fraumeni decided to look at another group that had received contaminated vaccine.

The group had been the subject of experiments conducted in the early 1960s at Cleveland Metropolitan General Hospital. To determine the effect of different amounts of the vaccines, researchers at the hospital inoculated newborns from mostly lower-income black families with doses ranging up to more than 100 times the dose recommended for adults.

The experiments took place over three years and involved 1,073 infants. Most were given Sabin oral vaccine later determined to contain SV40.

From 1976 to 1979, Fraumeni and his associates sent letters to the children - now age 17 to 19 - but fewer than half responded. The researchers found no SV40-related health problems from exposure to contaminated vaccine.

However, their 1982 report published in the New England Journal of Medicine acknowledged the study's limitations: A majority of the children had not responded; SV40-related cancers might take longer than 17 to 19 years to develop, and SV40 appears less likely to infect humans through the oral vaccine.

Nevertheless, they called their findings "reassuring and consistent with the prevailing view that SV40 is not carcinogenic in human beings."

Then they decided to end the study, citing "the mounting complexities and obstacles in tracing this particular group and the negative results to date."

The study's closure appeared to end the government's research into the virus. But a few years later there would be a tectonic shift in SV40 research.

First Discovery, 1988

In Boston, two researchers stumbled onto something disturbing.

Dr. Robert Garcea and his assistant, Dr. John Bergsagel, were using a powerful new tool called polymerase chain reaction, or PCR, to look for a pair of common human viruses in children's brain tumors.

But a different DNA footprint kept popping up in more than half the tumors. They finally realized they were seeing SV40.

For more than a decade, scientists had reported sporadic findings of SV40 - like proteins in human tumors. But the earlier tests were primitive and the results suspect. PCR, however, is capable of amplifying infinitesimal fragments of DNA, which makes detections far more credible.

The findings were troubling. The researchers noted in their published report that the children were too young to have received the contaminated vaccine. But somehow the virus had infected them and embedded itself in their tumors.

Mesothelioma, 1988

That same year, Dr. Michele Carbone was surprised to find a milky, rindlike tumor in a laboratory hamster at the National Institutes of Health in Bethesda, Md.

The animal was one of a group given an SV40 injection directly into their hearts. Sixty percent of those hamsters developed the fatal cancer called mesothelioma.

Carbone, a postdoctoral fellow at the institute, knew that SV40 caused tumors in hamsters but only in specific locations where large doses of virus were injected. Here the mesothelial membrane lining the lungs apparently became cancerous from minuscule amounts of SV40 shed by the tip of the needle on the way to the hamsters' hearts.

So he tried another experiment, this time injecting SV40 directly into the thin mesothelial walls of another group of hamsters. Within six months, every animal developed mesothelioma.

Carbone was puzzled. Mesothelioma is a rare cancer. Few human cases were reported before the 1950s, but its incidence had been increasing steadily, reaching several thousand cases a year in the United States by 1988.

Studies had linked mesothelioma to asbestos exposure - with tumors usually appearing many decades later. Yet 20 percent of victims had no asbestos exposure.

Carbone decided to use PCR to test 48 human mesotheliomas stored at the NIH.

He was stunned: 28 of them contained SV40.

More Cancers, 1996

PCR unleashed a wave of SV40 discoveries.

By the end of 1996, dozens of scientists reported finding SV40 in a variety of bone cancers and a wide range of brain cancers, which had risen 30 percent over the previous 20 years.

Then, Italian researchers reported finding SV40 in 45 percent of the seminal fluid samples and 23 percent of the blood samples they had taken from healthy donors.

That meant SV40 could have been spreading through sexual activity, from mother to child, or by other means, which could explain how those never inoculated with the contaminated vaccine, such as the Boston children, were being infected.

Government Assurances, 1996

At the National Cancer Institute in Bethesda, officials were growing increasingly concerned about the SV40 discoveries.

The findings were of particular interest to Fraumeni, who had been promoted to director of NCI's Division on Cancer Epidemiology and Genetics. His earlier studies concluding that SV40 posed little or no health risk were now under challenge.

But the scientific community was skeptical of the recent SV40 discoveries. As a potent carcinogen in lab animals, SV40 had been used for years as a tool to study cancer. Therefore, the powerful PCR test was suspected of finding stray SV40 fragments that might have contaminated laboratories.

So Dr. Howard Strickler, one of Fraumeni's epidemiologists, led a study using PCR on 50 mesotheliomas from Armed Forces hospitals across the country. And he found no SV40.

Although the findings bolstered the government's long-standing position that SV40 did not appear to be a health risk, federal officials decided to convene a conference on the virus.

In January 1997, 30 scientists gathered at the National Institutes of Health in Maryland. Garcea, Carbone and others presented their evidence showing SV40 in tumors and pleaded for research funding.

Strickler presented his mesothelioma study, as well as new research he had just completed, this time working with Fraumeni.

Their new study compared 20 years of cancer rates of people born between 1947 and 1963, and therefore likely to have been exposed to the contaminated polio vaccine, with people born after 1963, who they believed weren't exposed.

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