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SV-40
http://www.ccid.org/addviruses/sv40.htm
SV-40 is a small double stranded, circular DNA virus of rhesus
monkey origin. It is closely related to JC and BK viruses of
human origin. While BK virus may not cause human disease, JC
virus can cause a very severe brain illness in HIV infected
patients, that is called progressive multifocal
leukoencephalopathy or PML. SV-40 is also distanly related to
human papillomaviruses, some of which cause cervical cancers.
SV-40 infection is now widespread within the human population
almost certainly as a result of poliovaccine produced in rhesus
monkey kidney cells during the 1950s. A recent study showed
infection in 23% of blood samples from normal individuals. The
virus can also be detected in sperm fluid and is likely to be
passed congenitally to future generations (Martini et al. SV40
Early Region and Large T Antigen in Human Brain Tumors,
Peripheral Blood Cells, and Sperm Fluids from Healthy
Individuals. Cancer Research 56: 4820-4825, 1996). As the title
indicates this paper also confirms previous reports that SV-40
is present in a significant proportion of human brain tumors.
Other reports have shown SV-40 in human brain tumors, e.g.
Bergsagel et al. New England Journal of Medicine 326: 988-993,
1992. SV-40 has also been detected in a high proportion of human
mesotheliomas (Carbone et al. Oncogene 9: 1781-1790, 1994); and
in bone tumors called osteogenic sarcomas (Carbone et al.
Oncogene 1996).
FDA has been reluctant to act on reports of SV-40 but will have
to respond to forthcoming publications in the "New Yorker" and
"Money" magazines.
SV-40 contamination was detected in the rhesus monkey kidney
cells used to make poliovaccine as early as 1960. A Federal
employee, Dr. Bernice Eddy, decided on her own inititive, to
test extracts from the monkey kidney cells used to make
poliovaccine for possible cancer causing agents. She chose to
use newborn hamsters since these animals developed tumors with a
type of virus she and Sarah Stewart had discovered in mice and
named polyoma virus. The inoculated hamsters developed tumors
similar to those induced with polyoma virus. The results of Dr.
Eddy's unauthorized testing was meet with the same scorn and
indifference as her earlier warings that some of the initial
lots of Salk vaccine retained live poliovirus. Again, frustrated
by the unwillingness of her supervisors to act on her tumor
findings, Dr. Eddy went around channels and disclosed her
results in a 1990 scientific meeting. Her punishment was to be
taken off poliovaccine safety testing and prohibited for over a
year from submitting her work for publication.
Dr. Eddy's findings did however leak out and were replicated by
Drs. Sweet and Hilleman at Merck. Initially, Hilleman thought
the SV-40 problem would apply mainly to the live polio vaccines
developed by Dr. Sabin and used extensively in the Soviet Union.
He even suggested that the Russians would be no threat at the
upcoming 1962 Olympics because they would be dragging with
tumors (The Health Century by Edward Shorter). Unfortunately, it
was soon realized that the polio vaccine developed by Dr. Salk
was the more dangerous because the 1:4,000 dilution of
formaldehyde, which barely inactivated the poliovirus, did not
fully inactivate SV-40. Because the Salk vaccine was injected
through the skin, it allowed the SV-40 a better chance to
infect.
To his credit, Dr. Hilleman repeatedly sounded warnings about
the risks inherent in the use of monkey tissue for vaccine
production. For example, he has made the following comments "
...use of tissues of wild-caught animals is just asking for
trouble because of the lack of control and the known high
proability for viral contamination. Monkeys are too expensive to
be grown in specific pathogen-free colonies and, hence, the
simple solution to the monkey problem is to eliminate the
monkey" and also "The tissues of wild-caught animals, and
certainly monkeys, are commonly infected with wild viruses. The
simplest way to solve the monkey problem is to eliminate the
monkeys and this is being done using diploid cells. Monkey
tissues came into use by historic decisions to use monkey kidney
to make poliovaccine. There is no need to continue using monkeys
when acceptible alternatives are available. This advice was
never taken especially in the face of pressure from Lederle/American
Cyanamid to continue to use monkeys.
The main result of finding SV-40 virus in rhesus monkeys was
simply to switch poliovaccine production to African green
monkeys. Existing stocks of SV-40 poliovaccines were not
withdrawn from the market, nor was any effort made to suspend
the military's use of adenoviral vaccines, also known to contain
SV-40. Short termed follow studies on some of the children
exposed to SV-40, to see if brain tumors had developed,
satisfied those in charge of Public Safety, that no harm had
been done.
Since the hamster tumor model required virus exposure to newborn
animals, Public Health officials should have predicted the need
to maintain surveillance for the subsequent human generation.
Now that evidence is accumulating that a problem exists, the
continued reluctance of FDA to respond is, to say the least,
disappointing.
The overall story with SV-40 is being replicated with the
resistance of FDA and of Industry to meaningly address the
question of other monkey viruses having been transmitted to
humans through poliovaccines. While the African green monkey is
generally free of SV-40 virus, it does carry a number of
viruses, including simian cytomegalovitrus (SCMV). As an aside,
rhesus and not African green monkeys are used for testing the
virulence of live polio vaccines, because even the control
African green monkeys often show evidence of neural infection.
In an effort to underscore, the need for a more responsive FDA,
samples of a 1954 polio vaccine, held by Dr. Ratner, a Public
Health official whose concerns about poliovaccine safety had
been largely ignored, have been sent to investigators studying
SV-40 to show how easy it is to detect contaminants using the
PCR assay. This assays was not available in the 1950s, but now
that it is, there is no excuse for not using it on polio and
other vaccines to exclude contaminants including SCMV and
related stealth viruses.
A copy of Dr. Carbone's latest paper will be posted shortly.
Additional information can also be found in the Handouts under
Publications and Presentation section.
For information on SV-40 testing please refer to the Clinical
Laboratory.
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