The True Story of a Cancer-Causing Monkey Virus
<<< Back to Vaccines
LANCET Volume 364, Number 9432
31 July 2004
The Virus and the Vaccine: The True Story of a Cancer-Causing Monkey Virus,
Contaminated Polio Vaccine, and the Millions of Americans Exposed
Debbie Bookchin, Jim Schumacher. St Martin's Press, 2004. Pp 380. $25�95.
ISBN 0-31-227872-1.
On any list of medical triumphs of the 20th century, polio vaccination is
sure to rate a mention. In the 1950s and early 1960s, the shot and
sugar-cube vaccines of Jonas Salk, and later Albert Sabin, offered people
the first opportunities to protect themselves from a scourge as feared in
its day as AIDS is in our own.
Few back then grasped that these vaccines might also be a huge, inadvertent,
uncontrolled experiment in interspecies viral transmission. But from 1955 to
1963, according to a 1976 US National Institutes of Health (NIH)-funded
study, 98 million Americans alone probably were exposed to polio vaccines
contaminated with SV40--a monkey virus that can cause cancers in animals.
Now, a July 7 report in New Scientist has raised fears that hundreds of
millions of eastern Europeans, Asians, and Africans also may have been
exposed to SV40 in Soviet-made polio vaccines. Michele Carbone of Loyola
University Medical Center, Chicago, USA, announced at the 2004 Vaccine Cell
Substrates meeting (Rockville, MD) that the Soviet vaccine could have been
contaminated until the 1980s. This is worrying since, despite 44 years of
medical debate, epidemiological studies have yet to establish conclusively
whether SV40 has or hasn't caused cancers in people.
When Salk developed his vaccine, instead of using human tissues, as did the
scientists who won a Nobel Prize for first growing poliovirus in tissue
culture, he used minced-up rhesus macaque monkey kidneys, which were
remarkably efficient poliovirus factories. Those who sought to supplant
Salk's formaldehyde-inactivated vaccine with live, attenuated oral vaccine
also used monkey kidney cultures. Despite a manufacturing problem that, at b
est, left six children who received the vaccine paralysed in the arm, and
despite concerns about wild simian viruses, Salk's shots were declared safe
and effective after 1954 field trials. The next year, after grudging
approval by sceptical government regulators, free Salk shots were made
available throughout the USA.
By 1960, scientists and vaccine manufacturers knew that monkey kidneys were
sewers of simian viruses. Such contamination often spoiled cultures,
including those of an NIH researcher named Bernice Eddy, who worked on
vaccine safety. In 1959, fresh from co-reporting that the mouse polyoma
virus could cause cancer in other animals, Eddy tested the rhesus monkey
kidney substrate used to make polio vaccine. She injected 154 newborn
hamsters with extracts of the cell cultures: 109 developed tumours. Next,
she ground up three of the tumours and injected the residue into other
hamsters. The animals receiving injections from two of the three tumours
developed cancers. But when Eddy put the substance back into the monkey cell
culture, nothing happened, and she couldn't isolate the suspected virus.
In The Virus and the Vaccine: The True Story of a Cancer-Causing Monkey
Virus, Contaminated Polio Vaccine, and the Millions of Americans Exposed,
Debbie Bookchin and Jim Schumacher report that in 1960, when Eddy presented
her results to her boss, a polio vaccine champion named Joe Smadel, he was
livid and disbelieving: "Its implications--that something in the polio
vaccine could cause cancer--was an affront to his career." Her discovery
also threatened one of the USA's most important public-health programmes.
"By 1960, tens of millions of Americans had been vaccinated against polio,
and it was federal health policy that everyone should be vaccinated and
continue to receive Salk booster shots."
Eddy tried to get word out to colleagues but was muzzled and stripped of her
vaccine regulatory duties and her laboratory. However, two Merck
researchers, Ben Sweet and Maurice Hilleman, soon identified the rhesus
virus later named SV40--the carcinogenic agent that had eluded Eddy. In
1963, US authorities decided to switch to African green monkeys, which are
not natural hosts of SV40, to produce polio vaccine. In the mid-1970s, after
limited epidemiological studies, authorities concluded that although SV40
caused cancer in hamsters, it didn't seem to do so in people.
Fast forward to the 1990s: Michele Carbone, then at NIH, was working on how
SV40 induces cancers in animals. One of these was mesothelioma, a rare
cancer of the pleura thought in people to be caused mainly by asbestos. The
orthodoxy held that SV40 didn't cause human cancers. Emboldened by a 1992
NEJM paper that found DNA "footprints" of SV40 in childhood brain tumours,
Carbone tested human mesothelioma tumour biopsies at the National Cancer
Institute: 60% contained SV40 DNA. In most, the monkey virus was active and
producing proteins.
He published his results in Oncogene in May, 1994, but the NIH declined to
publicise them. Doubters at NIH developed epidemiological evidence that
showed no correlation between people who received potentially contaminated
polio vaccines and increased cancer rates. Others suggested that the SV40
DNA was a laboratory contaminant. On the first point, the US Institute of
Medicine reviewed all published epidemiological studies of SV40 and found
them inconclusive. Meanwhile, Carbone had moved to Loyola University. There
he discovered how SV40 disables tumour suppressor genes in human
mesothelioma, and published his results in Nature Medicine in July, 1997.
Studies in Italy, Germany, and the USA also showed associations between SV40
and human cancers.
Between 1997 and early 2003, say Bookchin and Schumacher, more than 25
published studies found SV40 in human mesotheliomas; 16 others found the
virus in brain and bone cancers, lymphomas, and other cancers and in kidneys
and peripheral blood. As of 2003, SV40 had been found in human tumours in 18
developed countries. Bookchin and Schumacher claim that the rates of
SV40-positive tumours seem highest in countries that used the greatest
amount of contaminated Salk polio vaccine, including the UK, USA, and Italy.
As the SV40 story illustrates, until scientists know that a virus exists in
cell cultures, they can't create a test to detect it and thus can't
eliminate it from vaccines grown on those cultures. Might other potentially
dangerous simian viruses lurk in primary monkey kidney cultures used for
polio vaccines? Such concerns were relieved in January, 2000, when
attenuated oral polio vaccine made since the 1950s by Lederle Laboratories
on primary monkey kidney cultures was removed from the US market. Since
wild-type polio cases had been eradicated in the USA in the mid-1970s, the
eight to ten cases of paralysis caused yearly by return to neurovirulence of
the live vaccine virus were finally deemed no longer acceptable. The vaccine
was replaced with Aventis Pasteur's killed polio vaccine grown on a well
characterised VERO monkey cell line. Thus the odds of further contamination
by unrecognised viruses are thought to have been greatly reduced.
Bookchin and Schumacher complain that since the era of Bernice Eddy the NIH
hierarchy has been consistently dismissive of evidence that SV40 from
vaccines may have caused human cancers. Officials who had previously said
SV40 was harmless were authorised to assess independent research that
challenged that conclusion: "Not surprisingly, they reaffirmed their own
previous wisdom." Accepting that SV40 is a human carcinogen, they continue,
raises questions about what the government response should be: "A
coordinated and extensive search for SV40 in other kinds of tumors, coupled
with far greater efforts to study how the virus causes tumors? A crash SV40
screening program among populations most likely to have been infected? . . .
An anti-SV40 vaccination campaign?" The problem, they continue, is that to
undertake any of these options the government would have to admit that it
should have acted sooner to protect public health.
In The Structure of Scientific Revolutions (University of Chicago Press,
1962) Thomas Kuhn suggests that paradigm shifts don't happen because
opponents are converted by evidence, but rather because one generation of
investigators and scientific leaders dies and is replaced by another. For
credible epidemiological studies confirming whether SV40 from polio vaccines
has caused human cancers, we may have to wait until a new generation is put
in charge of the USA's health research bureaucracy.
Tom Curtis
Back to top of Document
