Getting Tested for SV40
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Currently, the SV40 Cancer Foundation is setting up SV40 testing
with several prominent hospitals and laboratories.
Antibody testing using Enzyme-Linked Immunosorbent Assay (ELISA) – The ELISA test detects antibodies to SV40 and can determine if you have an SV40 infection now or have had a SV40 infection in the past. This test can be performed on blood, urine and other body fluids.
Detecting the presence of SV40 using Polymerase Chain Reaction (PCR) – PCR testing looks for the actual SV40 virus. This test can determine if you have an active SV40 infection. This test can be performed on blood, urine and other body fluids.
Tumor Testing – PCR can also be used to detect the presence of SV40 in human cancers using materials taken during surgery, biopsy or aspiration.
Source: sv40foundation.org
Treating SV40 Cancers
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The presence of SV40 in a cancer can have a dramatic impact in the efficacy of standard cancer therapies and may actually be a factor in stopping these treatments from providing a cure.
It is well documented that SV40 binds with tumor suppressor genes p53 and RB. These genes and their proteins are needed to drive a damaged cell towards apoptosis – programmed cell death. Apoptosis is a critical cellular function that stops the growth of tumors in man. (That is why they are called tumor suppressor genes.)
Cell-killing or cytotoxic therapies like chemotherapy and radiation utilize apoptosis. These therapies cause cellular DNA damage such as point mutations, strand breaks, and other disturbances to a cell’s DNA. This DNA damage, in turn, triggers the apoptosis which leads to cell death. In this way, chemo and radiation kill cells (cancer cells and healthy cells). However, when the large T antigen (Tag) of SV40 is present in a cancer cell it binds p53 and RB and stops these genes from working. There is no apoptosis. The result is that chemo and radiation kill healthy cells, but the cancerous cells infected with SV40’s Tag live on with even more mutations. This means that standard cancer therapies may only make a SV40 cancer more abnormal and aggressive and less responsive to standard cytotoxic therapies.
Knowing this, you would think that a patient who is diagnosed with a cancer associated with SV40 (i.e. brain cancers, mesothelioma, bone cancers, Non-Hodgkins Lymphoma, and thyroid cancers) would have their cancer tested for the presence of this virus. And, if the virus is present, the patient would be offered rational therapies. Unfortunately, this is not the case. There are no prospective tests or trials in which SV40 status is used in clinical decision-making. Instead, tumors are tested often after a patient has died to determine whether it contained SV40. At this point, there is no benefit to the patient.
Why is this the current situation? There are many reasons, but the biggest one is that SV40 is a problem that federal government authorities have not addressed responsibly because the government’s own vaccine programs are responsible for the spread of the virus throughout the western world. Federal authorities are so concerned about being blamed for unleashing a cancer-causing monkey virus that they would rather ignore its role in cancer than take the appropriate steps to develop rational therapies.
The bottom-line is that there is no treatment for SV40 positive cancers and if your cancer has SV40 it may be even less responsive to standard cancer treatments. To find out if you or your cancer is infected with SV40 click here.
Types of SV40 Associated Cancers
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Below are types of human cancers in which SV40 has been found. By clicking on the name, you will link to some study abstracts that provides additional details. Please note that this is not a comprehensive list of all SV40-associated cancers or all medical/scientific articles written about the detection of SV40 in cancer.
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Astrocytomas
Huang H., et al. Identification in human brain tumors of DNA sequences specific SV40 large T antigen. Brain Pathol 1999 Jan;9(1):33-42.
Zhen H.N., et al. Expression of the simian virus 40 large tumor antigen (Tag) and formation of Tag-p53 and Tag-pRb complexes in human brain tumors. Cancer 1999 15;86(10):2124-32.
Martini, F., et al. Simian Virus 40 Footprints in Normal Human Tissues, Brain and Bone Tumours of Different Histotypes; 1997. Brown F, Lewis AM (eds): Simian Virus 40 (SV40): A Possible Human Polyomavirus. Dev Biol Stand. Basel, Karger, 1998, vol 94, pp 55-66.
Krieg, P., et al. Episomal simian virus 40 genomes in human brain tumors Proc Natl Acad sci USA 1981 Oct;78(10):6446-50.
Anaplastic Astrocytoma
Huang H., et al. Identification in human brain tumors of DNA sequences specific SV40 large T antigen. Brain Pathol 1999 Jan;9(1):33-42.
Choroid Plexus Papilloma
Huang H., et al. Identification in human brain tumors of DNA sequences specific SV40 large T antigen. Brain Pathol 1999 Jan;9(1):33-42.
Zhen H.N., et al. Expression of the simian virus 40 large tumor antigen (Tag) and formation of Tag-p53 and Tag-pRb complexes in human brain tumors. Cancer 1999 15;86(10):2124-32.
Martini, F., et al. Simian Virus 40 Footprints in Normal Human Tissues, Brain and Bone Tumours of Different Histotypes; 1997. Brown F, Lewis AM (eds): Simian Virus 40 (SV40): A Possible Human Polyomavirus. Dev Biol Stand. Basel, Karger, 1998, vol 94, pp 55-66.
Wang, J and Garcea R.L., et al, Simian virus 40 DNA sequences in human brain and bone tumours. Brown F, Lewis AM (eds): Simian Virus 40 (SV40): A Possible Human Polyomavirus. Dev Biol Stand. Basel, Karger, 1998, vol 94, pp 13-21.
14 of 17 pediatric brain tumors (13 choroid plexus tumors, 3 ependymomas and 1 ganglioneuroma) were positive for SV40 regulatory region sequences. Butel, J.S., et al. Detection of authentic SV40 DNA sequences in human brain and bone tumors Brown F, Lewis AM (eds): Simian Virus 40 (SV40): A Possible Human Polyomavirus. Dev Biol Stand. Basel, Karger, 1998, vol 94, pp 23-32.
Lednicky, et al., Natural simian virus 40 strains are present in human choroid plexus and ependymoma Virology. 1995 Oct 1;212(2):710-7. tumors.
Ependymoma
Huang H., et al. Identification in human brain tumors of DNA sequences specific SV40 large T antigen. Brain Pathol 1999 Jan;9(1):33-42.
Zhen H.N., et al. Expression of the simian virus 40 large tumor antigen (Tag) and formation of Tag-p53 and Tag-pRb complexes in human brain tumors. Cancer 1999 15;86(10):2124-32.
Martini, F., et al. Simian Virus 40 Footprints in Normal Human Tissues, Brain and Bone Tumours of Different Histotypes; 1997. Brown F, Lewis AM (eds): Simian Virus 40 (SV40): A Possible Human Polyomavirus. Dev Biol Stand. Basel, Karger, 1998, vol 94, pp 55-66.
Wang, J and Garcea R.L., et al, Simian virus 40 DNA sequences in human brain and bone tumours. Brown F, Lewis AM (eds): Simian Virus 40 (SV40): A Possible Human Polyomavirus. Dev Biol Stand. Basel, Karger, 1998, vol 94, pp 13-21.
14 of 17 pediatric brain tumors (13 choroid plexus tumors, 3 ependymomas and 1 ganglioneuroma) were positive for SV40 regulatory region sequences. Butel, J.S., et al. Detection of authentic SV40 DNA sequences in human brain and bone tumors Brown F, Lewis AM (eds): Simian Virus 40 (SV40): A Possible Human Polyomavirus. Dev Biol Stand. Basel, Karger, 1998, vol 94, pp 23-32.
Lednicky, et al., Natural simian virus 40 strains are present in human choroid plexus and ependymoma Virology. 1995 Oct 1;212(2):710-7. tumors.
Gemistocytic Astrocytoma
Huang H., et al. Identification in human brain tumors of DNA sequences specific SV40 large T antigen. Brain Pathol 1999 Jan;9(1):33-42.
Glioblastoma
Huang H., et al. Identification in human brain tumors of DNA sequences specific SV40 large T antigen. Brain Pathol 1999 Jan;9(1):33-42.
Zhen H.N., et al. Expression of the simian virus 40 large tumor antigen (Tag) and formation of Tag-p53 and Tag-pRb complexes in human brain tumors. Cancer 1999 15;86(10):2124-32.
Martini, F., et al. Simian Virus 40 Footprints in Normal Human Tissues, Brain and Bone Tumours of Different Histotypes; 1997. Brown F, Lewis AM (eds): Simian Virus 40 (SV40): A Possible Human Polyomavirus. Dev Biol Stand. Basel, Karger, 1998, vol 94, pp 55-66.
Krieg, P., et al. Episomal simian virus 40 genomes in human brain tumors Proc Natl Acad sci USA 1981 Oct;78(10):6446-50.
Gliosarcoma
Huang H., et al. Identification in human brain tumors of DNA sequences specific SV40 large T antigen. Brain Pathol 1999 Jan;9(1):33-42.
Medulloblastoma
Huang H., et al. Identification in human brain tumors of DNA sequences specific SV40 large T antigen. Brain Pathol 1999 Jan;9(1):33-42.
Zhen H.N., et al. Expression of the simian virus 40 large tumor antigen (Tag) and formation of Tag-p53 and Tag-pRb complexes in human brain tumors. Cancer 1999 15;86(10):2124-32.
Krieg, P., et al. Episomal simian virus 40 genomes in human brain tumors Proc Natl Acad sci USA 1981 Oct;78(10):6446-50.
Meningioma
Zhen H.N., et al. Expression of the simian virus 40 large tumor antigen (Tag) and formation of Tag-p53 and Tag-pRb complexes in human brain tumors. Cancer 1999 15;86(10):2124-32.
Krieg, P., et al. Episomal simian virus 40 genomes in human brain tumors Proc Natl Acad sci USA 1981 Oct;78(10):6446-50.
Weiss A.F., et al. Simian virus 40-related antigens in three human meningiomas defined chromosome loss Proc Natl Acad Sci USA 1975 Feb;72(2):609-13.
Oligodendroglioma
Huang H., et al. Identification in human brain tumors of DNA sequences specific SV40 large T antigen. Brain Pathol 1999 Jan;9(1):33-42.
Krieg, P., et al. Episomal simian virus 40 genomes in human brain tumors Proc Natl Acad sci USA 1981 Oct;78(10):6446-50.
Pituitary Adenoma
Zhen H.N., et al. Expression of the simian virus 40 large tumor antigen (Tag) and formation of Tag-p53 and Tag-pRb complexes in human brain tumors. Cancer 1999 15;86(10):2124-32.
Osteosarcoma
Martini, F., et al. Simian Virus 40 Footprints in Normal Human Tissues, Brain and Bone Tumours of Different Histotypes; 1997. Brown F, Lewis AM (eds): Simian Virus 40 (SV40): A Possible Human Polyomavirus. Dev Biol Stand. Basel, Karger, 1998, vol 94, pp 55-66.
Wang, J and Garcea R.L., et al, Simian virus 40 DNA sequences in human brain and bone tumours. Brown F, Lewis AM (eds): Simian Virus 40 (SV40): A Possible Human Polyomavirus. Dev Biol Stand. Basel, Karger, 1998, vol 94, pp 13-21.
Ewing’s Tumors
Martini, F., et al. Simian Virus 40 Footprints in Normal Human Tissues, Brain and Bone Tumours of Different Histotypes; 1997. Brown F, Lewis AM (eds): Simian Virus 40 (SV40): A Possible Human Polyomavirus. Dev Biol Stand. Basel, Karger, 1998, vol 94, pp 55-66.
Mesothelioma
Cristaudo A, et al., SV40 enhances the risk of malignant mesothelioma among people exposed to asbestos: a molecular epidemiologic case-control study. Cancer Res. 2005 Apr 15;65(8):3049-52.
Pass HI, et al., Evidence of an important role for SV40 in mesothelioma. Thorac Surg Clin. 2004 Nov;14(4):489-95.
Carbone M, et al., New developments about the association of SV40 with human mesothelioma. Oncogene. 2003 Aug 11;22(33):5173-80.
Non-Hodgkins Lymphoma
Vilchez RA, et al., Simian virus 40 tumor antigen expression and immunophenotypic profile of AIDS-related non-Hodgkin's lymphoma. Virology. 2005 Nov 10;342(1):38-46.
Butel JS, et al., Association between SV40 and non-Hodgkin's lymphoma. Leuk Lymphoma. 2003;44 Suppl 3:S33-9.
Papillary Thyroid Carcinomas
Vivaldi, et al., Simian virus 40-like sequences from early and late regions in human thyroid tumors of different histotypes. J Clin Endocrinol Metab. 2003 Feb;88(2):892-9.
Anaplastic Thyroid Carcinomas (ATC)
Vivaldi, et al., Simian virus 40-like sequences from early and late regions in human thyroid tumors of different histotypes. J Clin Endocrinol Metab. 2003 Feb;88(2):892-9.
Source: sv40foundation.org
How SV40 Causes Cancer
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The SV40 is a type of polyoma virus. The term “poly” means many and “oma” means tumor. Its very name designates its ability to cause many types of cancers. The specific biological mechanisms by which SV40 transforms (turns cancerous) cells have been well studied since its discovery in the early 1960’s. In fact, there are volumes of scientific publications on this subject. Below is a brief outline of some of the mechanisms. Supporting documentation can be found through Medline by simply entering the term SV40 with the appropriate mechanism.
1. Telomerase activity
The telomere is a repetitive stretch of DNA found at each end of a chromosome. Telomeres are shortened each time a cell divides. This is the reason that normal cells can only divide roughly 50 times. An enzyme, telomerase, extends the telomere. Tumors cells often have telomerase activity which allows the cancer cells to divide without limit. SV40 infection leads to telomerase activity.
2. Binding to and inhibition of cellular p53 and retinoblastoma (RB) proteins
The p53 gene and the retinoblastoma (Rb) gene are tumor suppressor genes. They promote cell-cycle arrest (stop cells from dividing) when the cells are injured or damaged. Their ability to function properly is critical because their respective proteins stop the formation of tumors. The major SV40 oncoprotein is the Large tumor antigen (Tag). Tag binds to and inactivates cellular p53 and Rb. Therefore, the presence of SV40 stops these tumor suppressor genes from doing their job.
3. Inhibition of protein phosphatase 2A (PP2A)
Protein Phosphatase 2A (PP2A) plays a role in the critical cellular processes of protein synthesis, DNA replication, transcription, and metabolism. Small t antigen of SV40 comprises 174 amino acids. The region between residues 97-103 interacts with the PP2A. This interaction reduces the ability of PP2A to inactivate ERK1 and MEK1 protein kinases, resulting in stimulation of proliferation of cells.
4. Inhibition of tumor suppressor gene RASSF1A
Loss or altered expression of the RASSF1A gene has been associated with the pathogenesis of a variety of cancers, which suggests the tumor suppressor function of this gene. SV40 large tumor antigen (Tag) blocks RASSF1A.
5. Upregulation of Notch-1
Notch-1 is a key cell regulatory gene. Notch can either suppress or promote tumors depending on the cell type and context. Aberrant Notch signaling has been linked to a wide variety of tumors and the involvement of Notch signaling in several cancers has been well studied. SV40 infection of human mesothelial cells directly causes overexpression of Notch-1 which promotes cell cycle progression.
6. Upregulation of the MET oncogene
The activation of hepatocyte growth factor (HGF) receptor (Met) leads to cell growth and motility in cells of different origin. SV40 infection can cause Met activation.
7. Upregulation of insulin-like growth factor (IGF-1)
The insulin-like growth factor (IGF) receptor (IGF-IR) mediates the mitogenic, transforming, differentiating, and anti-apoptotic effects of the IGF ligands. SV40 upregulates IGF.
Source: sv40foundation.org
National Institute of Health Patent
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On October 6, 1999, an announcement appeared in the Federal Register which detailed an invention owned by the National Institute of Health (NIH). This invention called, “Adenoviral Vector Expressing a SV4OT Antigen Antisense RNA” is a method to treat “all cancers that express SV40 T antigen.” The invention uses antisense technology which is a way of directly attacking SV40.
Here is an example of the NIH making available for licensing a government owned invention that treats SV40 cancers by inactivating SV40. We would suggest that this demonstrates that at least some scientists in the government are aware that SV40 is a cause of these cancers. For if SV40 were not a cause, how would its destruction treat “all cancers that express SV40 T antigen?”
The present invention describes a method of treatment of cancer by administering a replication-deficient recombinant adenovirus comprising a nucleic acid that encodes an antisense rebonucleic acid to the SV40 T antigene. In addition, it provides methods for reducing the level of expression of SV40 T antigen, induction of apoptosis, effecting cell growth arrest, reducing the levels of proto-oncogene expression, unregulating pro-apoptotic proteins, maintaining normal levels of functional p53, and maintaining normal levels of functional Rb, p107, and p130. The types of cancers contemplated by this invention include.
Federal Register: October 6, 1999 (Volume 64, Number 193)][Notices]
[Page 54336-54338]From the Federal Register Online via GPO Access [wais.access.gpo.gov][DOCID:fr06oc99-109]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health Government-Owned Inventions; Availability for Licensing
AGENCY: National Institutes of Health, Public Health Service, DHHS.
ACTION: Notice. SUMMARY: The inventions listed below are owned by agencies of the U.S. Government and are available for licensing in the U.S. in accordance with 35 U.S.C. 207 to achieve expeditious commercialization of results of federally-funded research and development. Foreign patent applications are filed on selected inventions to extend market coverage[[Page 54337]]for companies and may also be available for licensing.
ADDRESSES: Licensing information and copies of the U.S. patent applications listed below may be obtained by writing to the indicated licensing contact at the Office of Technology Transfer, National of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: 301/496-7057; fax: 301/402-0220. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.
Adenoviral Vector Expressing a SV4OT Antigen Antisense RNA David S. Schrump, Z. Sheng Guo, Ishrat Wahseed (NCI) Serial No. 60/124,776 filed 17 Mar 1999Licensing Contact: Richard U. Rodriguez; 301/496-7056 ext. 287; e-mail: rr154z@nih.gov
Desired nucleic acid sequences with therapeutic potential may be introduced into mammalian cells using appropriate vectors. Antisense technology is well known in the art and describes a mechanism whereby a nucleic acid comprising a nucleotide sequences, which is in a complementary, "antisense" orientation with respect to a coding or "sense" sequence of an endogenous gene, is introduced into a cell, whereby a duplex forms between the antisense sequence and its complementary sense sequence. The formation of this duplex results in inactivation of the endogenous gene. The present invention describes a method of treatment of cancer by administering a replication-deficient recombinant adenovirus comprising a nucleic acid that encodes an antisense rebonucleic acid to the SV40 T antigene. In addition, it provides methods for reducing the level of expression of SV40 T antigen, induction of apoptosis, effecting cell growth arrest, reducing the levels of proto-oncogene expression, unregulating pro-apoptotic proteins, maintaining normal levels of functional p53, and maintaining normal levels of functional Rb, p107, and p130. The types of cancers contemplated by this invention include all cancers that express SV40 T antigen.
Sir Austin Bradford Hill
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In 1965, Sir Austin Bradford-Hill (1897-1991), a British medical statistician, established nine widely used criteria to determine the strength of an association between a disease and its supposed causative agent. These criteria are used as a way of determining the causal link between a specific factor (e.g., cigarette smoking, presence of SV40) and a disease (such as cancer).
Below are two examples of in which the Bradford-Hill criteria are applied to SV40. The first example focuses on mesothelioma and the second one focuses on brain cancer.
Bradford-Hill Criteria and Mesothelioma
In the article SV40 and Human Tumours: Myth, Association or Causality? the authors, Drs. Gazdar, Butel, and Carbone include a table in which they applied the Bradford-Hill criteria to SV40 and human papillomavirus (HPV). The HPV comparison is included because it represents a relationship that is universally accepted. This Table supports the position that the SV40 association with some human mesothelioma cancers is causative.
Table 1: SV40 and human mesothelioma – association or causation?
| Bradford-Hill Criterion | HPV and cervical cancer | SV40 and mesothelioma |
| Strength and association | The strength of association between HPV and cervical cancer is considered one of the strongest for a human cancer. Recent studies have shown that HPV (all types combined) is present in >90% of cervical cancers | Several studies have found evidence of SV40 in ~50% of human mesotheliomas, both in the United States and in some European countries |
| Consistency | The presence of HPV in cervical cancer is consistent among a large number of studies, regardless of the HPV testing system used. There are no published studies with negative observations that challenge the association of HPV and cervical cancer | At least 30 studies have reported SV40 in human mesotheliomas using a variety of techniques, whereas four have failed to find an association |
| Specificity | Specific cancers are related to the presence of HPV. HPV type is also important in the development of specific cancers. HPV is present in the tumour cells. Viral oncogene expression (E6 and E7) occurs in tumour material, but not in stromal cells | SV40 is present in a highly specific group of human tumours. Furthermore, injection of the virus into hamsters produces the same tumours. In human mesotheliomas, SV40 is found only in tumour cells and not in the surrounding non-malignant tissue |
| Temporality | HPV infections precede pre-cancerous cervical lesions and cervical cancer by years to decades | Little is known, although the virus has been found in preneoplastic lesions. The tremendous increase in the incidence of mesotheliomas over the past several decades was preceded by the administration of SV40-contaminated poliovirus vaccines, as well as by an increased exposure to asbestos |
| Biological gradient (dose-response) | Unclear, but early studies show that cervical cancer is associated with high viral loads | Unknown. Because humans are permissive to SV40, millions of SV40 particles are produced from few infected cells |
| Biological plausibility | HPV is a powerful carcinogen that immortalizes human keratinocytes in vitro. There are no animal models in which a sexually transmitted PV produces cervical cancer. HPV is present in cervical cancer, where it expresses the oncogenic proteins E6 and E7 that inactivate the host regulatory proteins p53 and RB, respectively. Epidemiological studies support a role for HPV in cervical cancer | SV40 is a powerful carcinogen that, in vitro, transforms human mesothelial cells. It induces mesothelioma development in hamsters. SV40 also expresses the oncogenic protein T Ag in human mesotheliomas, which inactivates p53 and RB. Definitive epidemiological studies are lacking |
| Biological coherence | The association does not conflict with what is known about the natural history of cervical cancer development | The association does not conflict with what is known about the natural history of mesothelioma, and it might explain why those with no history of asbestos exposure can develop the disease |
| Experimental evidence | In vitro and in vivo evidence supports a causal role for HPV in the development of cervical cancer | In vitro and in vivo evidence indicates a causal role for SV40 in mesothelioma development |
| Analogy | Other DNA tumour viruses can induce cancers in humans, and species-specific papillomaviruses can induce cancers in animals | Other DNA tumour viruses can induce cancers in humans, and SV40 induces mesotheliomas in animals |
Bradford-Hill Criteria and Brain Cancer
This section was written by one of us (Michael Horwin, MA, JD). His methodology was simply to apply what was published in the peer-reviewed medical literature to the nine Bradford-Hill criteria in respect to medulloblastoma and other brain cancers. The fifty-four citations that form the basis of this analysis can be found below.
Introduction
The rate of pediatric brain tumors is increasing and cytotoxic therapy (i.e. chemotherapy and radiation) is seldom successful in significantly prolonging life or curing the patient. To date, every type of pediatric brain tumor examined has been found to be positive for SV40 at statistically significant rates. The Bradford Hill criteria are comprised of nine aspects which can be used to help researchers determine if the association between a given virus and tumor is causal (e.g. does the virus cause or contribute to malignant transformation) or merely temporal. Below is a brief description of each of the nine criteria and the relevant data concerning SV40’s association with medulloblastoma and other pediatric brain cancers. The data demonstrates the strong possibility of a causal role of SV40 in the transformation and/or progression of these deadly tumors.
1. Consistency of findings across studies conducted with different methodologies and in different settings.
Although the data is limited because so few studies have been funded, every study that has looked for SV40 in human medulloblastomas has found it. In addition, different labs in different geographic regions of the world including the U.S., France and China have independently confirmed the presence of SV40 DNA in medulloblastoma.
Furthermore, SV40 has been found in every type of primary pediatric brain tumor examined including: meningioma, astrocytoma, choroid plexus papillomas and ependymomas. Thus, the available evidence indicates that SV40 is consistently involved in pediatric brain tumors including medulloblastoma.
2. Specificity in that the exposure precedes the effect and causes a particular disease, (e.g. the observation that cigarette smoking often precedes squamous cell carcinoma of the respiratory tract or Hepatitis B infection often precedes hepatocarcinoma).
Five epidemiological studies have demonstrated that exposure to SV40 precedes the increase in pediatric brain tumors including medulloblastoma. In each of these studies, the association between exposure to SV40 was statistically significant relative to the increase in pediatric brain tumors. These studies include the following:
In 1968, Innis found a significant association between immunization with the SV40 contaminated Salk vaccine and subsequent childhood malignancy.
In 1973, Heinonen et al. demonstrated an increased rate of tumors of neural origin in children exposed to SV40. This study reported a 12.7 times greater chance of a child getting cancer if his/her mother was vaccinated with killed polio vaccine containing SV40 while the child was in utero.
In 1979 and 1984 Farwell et al. demonstrated a higher number of medulloblastoma in children exposed to SV40. She reported that among medulloblastoma patients, 10 of 15 were exposed to SV40 and that this rate of exposure is higher and is significantly greater than among controls. In 1984 she reported that “…an excessive number of children born in the period 1954 to 1958 have developed medulloblastomas. A relationship to polio vaccine contaminated with SV40 may exist”.
In 1990, Geissler et al reported that patients with medulloblastoma had a greater likelihood of being exposed to SV40 from vaccine. His study demonstrated an increase of almost 30% in the number of medulloblastomas in a cohort of approximately 800,000 people.
In 1999, Fisher et al used SEER data to determine that there were increased rates of ependymomas (37%), mesotheliomas (90%) and other cancers in cohorts exposed to SV40 versus those who were not exposed.
In addition, PCR data suggests that SV40 DNA infection occurs early in tumor development. Using PCR-Southern hybridization, one study has demonstrated that in individual patients, the SV40 status of high-grade glioblastomas is similar to the status of the original tumors (lower grade astrocytomas) that gave rise to the glioblastoma. This suggests that SV40 DNA infection occurs “during early stages of tumor development rather than being associated with glioma progression”. Another study using transgenic mice has demonstrated that SV40 antigen is present before detectable pathology of SV40 transformed cells. This also suggests that exposure to SV40 precedes the genesis of the tumor.
3. Strength of the association examines what proportion of tumors are shown to contain the virus.
As mentioned above, although limited studies have been conducted, every PCR or immunohistochemistry test conducted on various human medulloblastoma tissues samples has found the presence of SV40 in a significant percentage (from 100% (1 out of 1) to 29%). In addition, every type of pediatric brain tumor tested has been demonstrated to be SV40 positive. As Table 2 indicates, these percentages, although varying, are significant:
| Table 2 | % positive (reference) | % positive (reference) | % positive (reference) | % positive (reference) |
| medulloblastoma | 29% | 33% | 100% | 50% |
| ependymomas | 56% | 91% | 100% | 75% |
| choroid plexus | 38% | 50% | 83% | |
| astrocytomas | 73% | 47% | ||
| meningioma | 43% | 31% | 100% | 19% |
| oligodendrogliomas | 10% | 33% | ||
| mix of pediatric brain tumors | 82% |
4. Temporal relationship considers if there is a relationship in time between the virus and the tumor.
The increasing incidence of medulloblastoma and other pediatric brain cancers in the United States has been preceded by the administration of SV40 contaminated polio vaccines. According to one published report the “rising childhood cancer rate represents a far more serious problem in the United States than previous reports have suggested”. Furthermore, SV40 has infected humans mainly through contaminated polio vaccines. Finally, significant differences in the incidence of medulloblastoma has been associated with exposure to SV40.
5. Dose-response relationship examines the relationship between the dose of the virus and the response of the host.
Uniform doses of SV40 produce higher percentage of tumors in younger animals. For example, the younger the animal was when exposed to SV40 the greater the percentage of tumors. In one study, over 95% of newborn and less than 2-day-old suckling hamsters developed tumors after being injected with SV40. When hamsters were inoculated at 7 or 8 days of age, about 60% still developed tumors. The animals remained susceptible to the oncogenic potency of SV40 up to 3 weeks of age, but the incidence of tumors was substantially lower in the older groups. According to this researcher, “The observation that a latent virus indigenous in monkey kidney cells, and apparently harmless for its carrier host species, can induce a high incidence of malignant, progressively growing tumors when inoculated into newborn animals of another species is striking”.
6. Coherence of epidemiological evidence: the geographically widespread association of SV40 DNA with human medulloblastoma is consistent with the widespread vaccination of large numbers of children with SV40 contaminated polio vaccines.
7. Biological plausibility: the well-recognized oncogenic properties of the SV40 virus in a variety of animal bio-assays (see below) and in vitro human cell culture studies, its capacity to survive and replicate in infected human subjects for prolonged periods, its ability to create brain tumors via subcutaneous injections in animals, its capacity to be carried through the blood and infect the brain, and its particular affinity for human brain cells, support its potential to cause tumors in susceptible children.
SV40 can transform human cells in vitro, causing chromosomal aberrations, aneuploidy and point mutations: SV40 is an oncogenic virus capable of transforming cells of different species, including human cells in vitro. This has been known for over 40 years. In 1962, “Koprowski and his colleagues…inoculated organ cultures prepared from human skin and buccal mucosa, with SV40. A transformation could be observed in the infected cell cultures 8 to 14 weeks after exposure to the virus…these cells eventually spread and overgrew the normal cell population. Distinct chromosomal abnormalities accompanied this cell transformation”. In addition, a number of other studies have independently demonstrated this association or cited this well-known capacity. Furthermore a recent report published by the NCI demonstrated that an adenoviral vector expressing an antisense transcript to SV40 inhibited T antigen expression and mediated “significant growth inhibition and apoptosis in malignant pleural mesotheliomas.” This effect was not observed in mesotheliomas containing no SV40 sequences. The authors concluded that these data “suggest that SV40 oncoproteins contribute to the malignant phenotype of pleural mesotheliomas…”
SV40 has the capacity to replicate in humans. Human exposure to SV40 and subsequent excretion of the virus for several weeks indicates that the virus has the ability to replicate in humans. This has been known for nearly 40 years.
SV40 creates brain tumors via subcutaneous injection in animals. SV40 has been demonstrated to create brain tumors with significant consistency (80%) in laboratory animals when injected via subcutaneous inoculation without the development of either subcutaneous or visceral neoplasms resulting from such an inoculation.
SV40 is carried through the blood to infect target organs such as the brain in humans. Experimental evidence suggests that human peripheral blood cells and B and T-lymphocytes are vectors for the transfer of SV40 to other human tissues of the host.
SV40 has a particular affinity for human brain cells. SV40 is known to replicate in certain human glial cells and this suggests that these cells have a functional SV40 receptor.
8. Reasoning by analogy: SV40 is a proven cancer virus, based on experimental animal model systems, analogous tumor systems, in vitro transformation studies involving human cells (see above), and its well-known capacity to bind suppressor genes (see below).
SV40 can create medulloblastoma in animals. SV40 has been shown to cause medulloblastoma-like PNET’s in rats using retrovirally transduced SV40 large Tag.
SV40 has also been demonstrated to cause primitive neuroectodermal type tumors (PNET’s) in transgenic mice.
Analogous tumor systems. SV40 may act as a cofactor in human carcinogenesis particularly medulloblastomas, much like EBV in Burkitt’s lymphoma and nasopharynx carcinoma or hepatitis B virus in hepatocarcinoma. In addition, HPV and JC viruses, which share capacity to bind and inhibit p53 and Rb proteins, have been causally linked to cervical cancer and brain tumors, respectively.
9. Experimental evidence demonstrates that SV40 can grow better in human fetal brain cells than other human cells, affect changes in human chromosomes, bind human tumor suppressor genes, and is detected in the tumor cells but the adjacent normal tissue is devoid of viral DNA. In addition, there is genetic and pathological evidence to support the hypothesis that human pre-cursor brain cells may be infected by SV40 and produce medulloblastoma and that SV40 DNA infection occurs early in brain tumor development.
SV40 grows better in human fetal brain cells than human fetal kidney cells or fibroblasts. In a study that examined the infection rates of SV40 in human fibroblasts, human embryonic kidney cells, and human fetal brain cells, it was demonstrated that the most “robust” growth took place in brain cells. The infection rate was as productive as that found in the highly related human BK virus.
SV40 can affect changes in human chromosomes. It has been demonstrated that SV40 Tag can induce chromosomal aberrations in normal human cells.
SV40 binds human tumor suppressor genes. SV40 binds the products of p53 and p105 RB tumor suppressor genes leading to their functional inactivation which causes or contributes to oncogenic transformation.
Adjacent normal tissue devoid of viral DNA. SV40 large T antigen sequences have been found in the brain tumors investigated but not in the adjacent healthy brain tissue.
Pre-cursor brain cells may be infected by SV40 and produce medulloblastoma. It is thought that large Tag induced PNET’s (i.e. medulloblastomas) arise from a subpopulation of precursor cells which are susceptible to transformation by Tag. Through inactivation of Rb, these cells retain their proliferative and migratory capability and that inactivation of p53 allows for the establishment and accumulation of genetic alterations that prevent apoptosis leading to medulloblastoma.
Conclusion
The epidemiological, biological, genetic, and experimental data present a strong case for the role of SV40 in causing or contributing to the transformation and oncogenic progression of human brain tumors. There is more data on the plausible carcinogenic role for SV40 than for many other substances and agents that have been deemed anticipated or known human carcinogens by IARC, EPA and OSHA.
Currently, there are no comprehensive studies in the U.S. examining the role SV40 may play in pediatric brain cancer or any brain cancer for any age group. This is due to a lack of governmental interest in funding this research perhaps because the virus was introduced into the human population via contaminated vaccines. The fear of liability on the part of the government and the vaccine manufacturer’s has resulted in the virtual paralysis of research in this area.
Orthodox cancer therapy is the only treatment legally permitted to be administered to children with cancer. If parents desire other modalities, at the oncologist’s behest, children may be taken from their parents so that cytotoxic therapies (radiation and chemotherapy) can be administered without parental permission. Beyond, the moral and ethical questions raised by such actions, there is compelling scientific evidence to suggest that such conduct is medically irresponsible. As cited above, SV40 is known to induce oncogenic transformation by forming complexes with critical tumor suppressor genes such as p53. However, it is these very tumor suppressor genes that cytotoxic therapy depends on in order to initiate cellular apoptosis. If the cells’ tumor suppressor genes and their corresponding proteins can not be expressed appropriately then cell-killing therapy is significantly handicapped. The presence of SV40 can ensure that chemotherapy and radiation will have negligible efficacy. The fact that a significant percentage of pediatric brain tumors are positive for SV40 and a significant percentage of pediatric brain tumor patients will reap no benefit from orthodox cytotoxic therapy may not be coincidental. There is strong scientific evidence that oncologists are sentencing thousands of children to ineffective, debilitating and toxic cancer therapies that do nothing more than insure their death and fill their last months alive with needless misery and pain.
Experts Opinion
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In 2002, three leading SV40 experts (Drs. Gazdar, Butel and Carbone) who have been involved in studying SV40 for a number of years wrote:
“[1]t is our opinion that SV40 should be included in the list of group 2A carcinogens – that is, those that are probably carcinogenic to humans.”
-- Gazdar AF, Butel JS, Carbone M., SV40 and human tumours: myth, association or causality? Nat Rev Cancer. 2002 Dec;2(12):957-64.
This group (2A) is part of the classification scheme provided by the International Agency for Research on Cancer (IARC), which is part of the World Health Organization. IARC’s mission is to coordinate and conduct research on the causes of human cancer, the mechanisms of carcinogenesis, and to develop scientific strategies for cancer control. IARC also publishes a monograph series that provides a ranking system for carcinogenic substances.
Group 1: The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans.
Group 2A: The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans.
Group 2B: The agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans.
Group 3: The agent (mixture, or exposure circumstance) is not classifiable as to carcinogenicity in humans.
Group 4: The agent (mixture, exposure circumstance) is probably not carcinogenic to humans.
Substances in Group 2A include a number of toxic chemotherapy drugs, viruses, and other recognizable substances. Examples include:
Chemotherapy in Group 2A
Adriamycin
Bischloroethyl nitrosourea (BCNU)
Cisplatin
Etoposide
Nitrogen mustard
Procarbazine hydrochloride
Teniposide
Viruses in Group 2A
Human papillomavirus types 31, 33
Kaposi's sarcoma herpesvirus/human herpesvirus 8
Recognizable Substances
Lead compounds, inorganic
Ultraviolet radiation
Creosotes (from coal-tars)
How OPV was Produced
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Once their polio seeds were isolated, pharmaceutical companies needed a method to propagate the viruses in order to produce the vast quantities of vaccine needed for nation-wide immunization campaigns. This required a medium or substrate upon which the poliovirus could be efficiently grown and harvested. Kidney cells from rhesus monkeys were chosen because they were found to be an effective growth medium. A small quantity of poliovirus could be added to the minced kidneys surgically removed from these monkeys and within a few days, large quantities of poliovirus could then be harvested from these same monkey cells.
There was a problem, however, with using these monkey kidney cells to both create the original vaccine strains and grow the vaccine in large quantities. Monkeys contain simian viruses. And the monkeys they used (i.e. rhesus and African Greens) are known carriers of SV40. When the poliovirus was passaged through these monkeys or grown on the monkey kidney cells for production, extraneous viruses became part of the final poliovirus vaccine. As early as 1953, Dr. Herald R. Cox, a scientist working at Lederle Laboratories, one of the polio vaccine manufacturers, published an article in a peer reviewed scientific journal in which he stated:
“[P]oliomyelitis virus has so far been cultivated only in the tissues of certain susceptible species—namely, monkey or human tissues. Here again we would always be confronted with the potential danger of picking up other contaminating viruses or other microbic agents infectious for man.”
In fact, in 1958, a scientific journal reported that “the rate of isolation of new simian viruses (from monkey kidney cells) has continued unabated.” Additionally, in 1960, the pharmaceutical company Merck & Co. wrote to the U.S. Surgeon General:
“Our scientific staff have emphasized to us that there are a number of serious scientific and technical problems that must be solved before we could engage in large-scale production of live poliovirus vaccine. Most important among these is the problem of extraneous contaminating simian viruses that may be extremely difficult to eliminate and which may be difficult if not impossible to detect at the present stage of the technology.”
How OPV Seed was Created
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The seed is the original polio vaccine material created by Drs. Sabin and Salk that would be used to make all subsequent polio vaccines for decades. The creation of these seeds explains how they became contaminated with SV40.
As you read this, keep in mind that rhesus monkeys are known carriers of SV40 and African Green monkeys can also be a carrier, but less frequently. The term “passaging” is also important. It means introducing a virus into a living being (i.e. by oral, nasal, inoculation) and then harvesting that virus after it has multiplied and adapted itself to that host. Passaging can make a virus less virulent.
In the 1950s, scientists like Doctors Jonas Salk and Albert Sabin had isolated the poliovirus strains to make vaccines. Dr. Salk’s strains would be inactivated with formaldehyde and injected into children. Dr. Sabin’s strains would be attenuated or weakened by transferring or passaging the live viruses through different host cells and then fed to children orally.
Because his goal was to create a live attenuated vaccine, Dr. Sabin had to isolate the poliovirus strains and then passage the strains through a myriad of host cells in order to attain the right virulence—strong enough to illicit an immune response, but weak enough so as to not cause polio in the recipient. Sabin’s oral polio vaccine (OPV) is a trivalent vaccine and was, therefore, comprised of three types – Type I, II, and III.
For example, Type I has the following lineage: In 1941, Drs. Francis and Mack isolated the Mahoney poliovirus “from the pooled feces of three healthy children in Cleveland.” Dr. Salk then subjected the strain to passages through fourteen living monkeys and two cultures of monkey testicular cultures. In 1954, the strain (now called Monk14 T2) was given to Drs. Li and Schaeffer who subjected the virus to nine more passages through monkey testicular cultures. Next, the strain (now called Monk14 T11) underwent fifteen more passages in monkey testicular cultures, eighteen passages in monkey kidney cells, two passages through the skin of living rhesus monkeys, and additional passages through African Green monkey skin and monkey kidney cell cultures. This strain was now called MS10 T43 or LS-c. In 1956, Dr. Sabin took this virus and passaged it through seven cultures of African Green Monkey kidney cells. That same year, the pharmaceutical company, Merck, Sharp & Dohme, passed the strain (now called LS-c, 2ab/KP2) through a rhesus monkey kidney cell culture. The resulting material was called Sabin Original Merck (SOM) and was provided to Lederle in 1960 as the seed material to manufacture its polio vaccine. Types II and III were created in a similar fashion.
Source: sv40foundation.org
Have polio vaccines been responsible for the spread of SV40 throughout the population?
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The answer is “yes.”
To better understand the question and the answer it is important to recognize three distinct time periods:
Prior to 1961
All health authorities agree that both the Salk Inactivated Polio Vaccine (IPV) and Sabin Oral or “live” Polio Vaccine (OPV) were contaminated with SV40 up until 1961. The contamination has been estimated to have exposed up to 30 million Americans and millions more in the USSR (where the OPV clinical trials were conducted) and other countries. In 1961, federal regulations went into effect in the U.S. (and similar regulations went into effect in other parts of the world) that required that polio vaccines be free of SV40. The new regulations in the U.S., however, did not require that: 1) the SV40 contaminated seeds used to make every “batch” or “lot” of vaccine be discarded; 2) the recently manufactured contaminated vaccines be discarded.
1961-1963
In the U.S., federal law did not require that SV40 contaminated vaccines be discarded if they were manufactured before the new regulations went into effect. This meant that vaccines contaminated with SV40 were administered to children and adults until they were used up. This is estimated to have happened some time in 1963. Millions of people were unnecessarily exposed to SV40 because of economic pressures (the vaccine manufacturers did not want to throw away millions of vaccine vials) and political concerns about the public’s trust in the government’s polio vaccine campaign. (The federal government did not want publicity about manufacturing problems related to polio vaccines especially after the so-called Cutter incident in which children were reportedly paralyzed and killed from virulent polio vaccines.)
After 1963
What happened after 1963 is debated. Government authorities believe that there were no contaminated vaccines released after this period. Others think that this is not the case. The argument comes down to two sets of evidence: 1) what was actually done by the manufacturers to ensure that SV40 was removed; 2) what various studies have revealed.
Obviously, the best way to answer this question is for the government to demand (or for manufacturers to volunteer) to open their freezers and allow independent SV40 scientists to test the vaccine materials in cold storage. Given the public health implications one would think that such steps should have been undertaken years ago. They have not. The government has never demanded that independent testing be performed and the manufacturers have never volunteered.
IPV versus OPV
After 1961, IPV was no longer grown on monkey kidney cells taken straight from monkeys. Instead it was grown on Vero cells, a continuous line of monkey kidney cells that are grown for the express purpose of providing an advantageous agent-free cell culture medium. In addition, other steps had been implemented that would help prevent SV40 contamination in IPV. These steps included the addition of the required amount of formalin and the use of column chromatography. In contrast, the oral polio vaccine was still grown on primary monkey kidney cells (kidneys removed from live monkeys) and there was no evidence that the original contaminated poliovirus seed stocks were ever replaced. Therefore, the following discussion will focus on OPV.
What was Done by Manufacturers to Ensure SV40 Removal
A) The OPV manufacturers allegedly introduced rabbit anti-SV40 antibodies into their seeds.
The SV40 contaminated seeds were used to manufacture all subsequent polio vaccines for the next 40 years. Rabbit anti-serum was added to the seeds. It was theoretically designed to eliminate the SV40. There are a number of problems with this approach, however, including:
The methodology as to how this was performed has never been made publicly available for scientists to assess.
Testing to determine the success of this methodology (whether it worked) has never been made publicly available.
Testing to determine whether the antibody actually removed SV40 has never been made publicly available. (In fact, most antibodies bind to viruses flagging them for consumption by other cells. Antibodies themselves may not physically remove a virus.)
In essence, we are told that the anti-serum worked to remove infectious SV40 without any proof whatsoever.
B) The OPV manufacturers also used an infectivity test to look for SV40 during production.
Manufacturers initiated government-mandated testing that was based on infectivity assays. In essence, they took the monkey kidney cells upon which the vaccine would be grown and:
1) Looked at them through a microscope to see if they demonstrated SV40;
2) Took fluids from them;
3) Introduced those fluids into other cell cultures;
4) Waited 14 days;
5) Saw whether the other cell cultures were changed as a result of the presence of SV40.
6) Recultured and repeated.
These tests were not designed to detect the contaminating viruses themselves. One cannot see SV40 or any virus with a standard light microscope or the naked eye. Instead, this test relied on the observation of the presumed effect of an SV40 infection on certain tissue cells to demonstrate the presence of the virus.
There are several problems with this, but the most glaring is that there never has been a single independent study that has confirmed that such testing is sufficiently sensitive to reliably detect all SV40. Instead, we have just the opposite. There have been many studies performed in the early 1960’s (right after these tests went into effect) that proved that the testing would not detect SV40 with any reliability. See SV40 Chronology for examples.
In addition, in December 1999, one of the leading SV40 scientists Michele Carbone, Ph.D., M.D., tested contaminated polio vaccines from 1955 and found that the vaccines contained more than one strain of SV40. The new strain he detected was slow-growing and would take at least nineteen days to appear in cell culture, five days past the federally mandated 14-day observation period. Dr. Carbone and his colleagues wrote that his study suggested that any slow-growing SV40 present in the vaccine would have gone undetected. The scientists also wrote, “they were surprised to learn” that more sophisticated techniques were not used to screen polio vaccines for SV40. (Paola Rizzo et al., Unique Strains of SV40 in Commercial Poliovaccines from 1955 Not Readily Identifiable with Current Testing for SV40 Infection, 59 CANCER RES. 6103, 6103–08 (1999))
C) The OPV manufacturers allegedly used monkeys that were free of SV40 for production.
Again, we are told this without any proof whatsoever. In fact, like rhesus monkeys, African Green Monkeys can harbor SV40.
What Various Studies Have Revealed
The government has never demanded that statistically valid independent testing be performed and the manufacturers have never voluntarily opened their freezers to allow such testing. Therefore, there have been no comprehensive studies to determine whether SV40 has been present in some “batches” or “lots” of OPV after 1963. The few studies that have been performed have an enormous number of questions about how they were done. One recent example will illustrate:
On November 15, 2005 an article entitled Some Oral Poliovirus Vaccines Were Contaminated with Infectious SV40 after 1961 appeared in the journal Cancer Research. It essentially is comprised of two studies:
One study purportedly examined the “current or recent seed lots of all three poliovirus serotypes from Belgium, Canada, France, Germany, Indonesia, Iran, Japan, Mexico, United Kingdom, United States, EEVM, Vietnam, and the former Yugoslavia as well as WHO seed viruses.” These seed lots were “tested at the NIBSC.” The NIBSC is the United Kingdom’s National Institute for Biological Standards and Control which has many of the same responsibilities as the National Institute of Health and the FDA in the United States.
According to the study, “The samples tested consistently negative, except that the EEVM vaccine produced positive PCR signals…” EEVM is a manufacturer in Eastern Europe whose OPV was “widely used in many countries, including the USSR, the countries of eastern Europe, Asia, and Africa.”
So, here we have the major health authority in the U.K. saying that all polio vaccine manufacturers they tested were free of SV40 except for one in Eastern Europe that supplied vaccines to many countries other than Western Europe and the U.S. This, of course, is a very convenient result.
How thorough was this testing? Here’s what we do not know:
The methodology is referred to from a previous paper, but that methodology does not even include a test to determine whether the vaccine they were testing was polio vaccine. So we do not know what they were testing.
They state that they tested the “current or recent seed lots…” What does that mean? Did they test actual seeds (the parent material) or working seeds (the progeny)? How much did they test? How many milliliters? Was it statistically valid and if so where is the statistical analysis?
They state that they tested “all three poliovirus serotypes from Belgium, Canada, France, Germany, Indonesia, Iran, Japan, Mexico, United Kingdom, United States, EEVM, Vietnam, and the former Yugoslavia as well as WHO seed viruses…” They don’t say which manufacturers they tested. They don’t say what materials they tested. They don’t say how much they tested.
If a first year graduate student was to write-up a study like this no doubt they would get an “F.” But, this is the quality of the work that a major governmental body uses when it comes to SV40 and vaccines. The result in this paper is that the spread of SV40 is blamed on a major eastern European vaccine manufacturer whose vaccine did not come into the U.S. or U.K., and other vaccine manufacturers such as those in the U.S. and U.K. are off the hook.
As bad as this first study is, the second one is good. After the NIBSC found SV40 in the vaccines from the major eastern European vaccine manufacturer they shipped it off to independent labs, including Dr. Carbone at Loyola University in Chicago. There, Dr. Carbone’s group put the EEVM positive samples through a battery of tests including PCR, transfection, and direct infection of susceptible cell cultures. His analysis confirmed the presence of SV40 and even identified the strains. In discussing one of the strains, Dr. Carbone wrote, “The other strain that we detected, CPC-MEN, was originally isolated in 1984 from a human brain tumor in a German patient. The same virus was independently isolated from a brain tumor of a U.S. patient in 1995.” Here, there is evidence that a specific type of SV40 from the polio vaccine was found in human brain tumors in Europe and the U.S.
This is important information. The larger question, however, is why didn’t the NIBSC send all of its samples from “current or recent seed lots” of all three poliovirus serotypes from Belgium, Canada, France, Germany, Indonesia, Iran, Japan, Mexico, United Kingdom, United States, Vietnam, the former Yugoslavia and the World Health Organization to Carbone and other labs for independent analysis and confirmation? The answer to this question is telling.
This is the current status of studies on this question. Government laboratories and labs tied to vaccine manufacturers or government funding report that they tested various polio vaccines for SV40 and for the major western manufacturers everything is okay. These governmental sponsored studies, however, never allow their results to be independently verified as required by the scientific method.
Source: sv40foundation.org
Simian Virus 40 (SV40): A Cancer Causing Monkey Virus from FDA-Approved Vaccines
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The Creation and Production of the Polio Vaccines
In the 1950s, scientists like Doctors Jonas Salk and Albert Sabin had isolated the poliovirus strains to make vaccines. Dr. Salk’s strains would be inactivated with formaldehyde and injected into children. Dr. Sabin’s strains would be attenuated or weakened by transferring or passaging the live viruses through different host cells and then fed to children orally.
Because his goal was to create a live attenuated vaccine, Dr. Sabin had to isolate the poliovirus strains and then passage the strains through a myriad of host cells in order to attain the right virulence—strong enough to illicit an immune response, but weak enough so as to not cause polio in the recipient. Sabin’s oral polio vaccine (OPV) is a trivalent vaccine and was, therefore, comprised of three types - Type I, II, and III. For example, Type I has the following lineage: In 1941, Drs. Francis and Mack isolated the Mahoney poliovirus “from the pooled feces of three healthy children in Cleveland.” Dr. Salk then subjected the strain to passages through fourteen living monkeys and two cultures of monkey testicular cultures. In 1954, the strain (now called Monk14 T2) was given to Drs. Li and Schaeffer who subjected the virus to nine more passages through monkey testicular cultures. Next, the strain (now called Monk14 T11) underwent fifteen more passages in monkey testicular cultures, eighteen passages in monkey kidney cells, two passages through the skin of living rhesus monkeys, and additional passages through African Green monkey skin and monkey kidney cell cultures. This strain was now called MS10 T43 or LS-c. In 1956, Dr. Sabin took this virus and passaged it through seven cultures of African Green Monkey kidney cells. That same year, the pharmaceutical company, Merck, Sharp & Dohme, passed the strain (now called LS-c, 2ab/KP2) through a rhesus monkey kidney cell culture. The resulting material was called Sabin Original Merck (SOM) and was provided to Lederle in 1960 as the seed material to manufacture its polio vaccine. Types II and III were created in a similar fashion.
Once their strains were isolated, pharmaceutical companies needed a method to propagate the viruses in order to produce the vast quantities of vaccine needed for nation-wide immunization campaigns. This required a substrate upon which the poliovirus could be efficiently grown and harvested. Kidney cells from rhesus monkeys were chosen because they were found to be an effective growth medium. A small quantity of poliovirus could be added to the minced kidneys surgically removed from these monkeys and within a few days, large quantities of poliovirus could then be harvested from these same monkey cells.
There was a problem, however, with using these monkey kidney cells to both create the original vaccine strains and grow the vaccine in large quantities. Monkeys contain simian viruses. When the poliovirus was passaged through the monkeys or grown on the monkey kidney cells for production, extraneous viruses became part of the final poliovirus vaccine. As early as 1953, Dr. Herald R. Cox, a scientist working at Lederle Laboratories, one of the polio vaccine manufacturers, published an article in a peer reviewed scientific journal in which he stated, “[P]oliomyelitis virus has so far been cultivated only in the tissues of certain susceptible species—namely, monkey or human tissues. Here again we would always be confronted with the potential danger of picking up other contaminating viruses or other microbic agents infectious for man.” In fact, in 1958, a scientific journal reported that “the rate of isolation of new simian viruses (from monkey kidney cells) has continued unabated.” Additionally, in 1960, the pharmaceutical company Merck & Co. wrote to the U.S. Surgeon General:
Our scientific staff have emphasized to us that there are a number of serious scientific and technical problems that must be solved before we could engage in large-scale production of live poliovirus vaccine. Most important among these is the problem of extraneous contaminating simian viruses that may be extremely difficult to eliminate and which may be difficult if not impossible to detect at the present stage of the technology.
The Discovery of Simian Virus 40 (SV40)
Between 1959 and 1960, Bernice Eddy, Ph.D., of the National Institute of Health (NIH) examined minced rhesus monkey kidney cells under a microscope. These were the cells of the same species of monkeys used to create and produce the oral polio vaccine. Dr. Eddy discovered that the cells would die without any apparent cause. She then took suspensions of the cellular material from these kidney cell cultures and injected them into hamsters. Cancers grew in the hamsters. Shortly thereafter, scientists at the pharmaceutical company Merck & Co. discovered what would later be determined to be the same virus identified by Eddy. This virus was named Simian Virus 40 or SV40 because it was the 40th simian virus found in monkey kidney cells.
In 1960, Doctors Benjamin Sweet and Maurice Hilleman, the Merck scientists who named the virus SV40, published their findings:
Viruses are commonly carried by monkeys and may appear as contaminants in cell cultures of their tissues, especially the kidney . . . . The discovery of this new virus, the vacuolating agent, represents the detection for the first time of a hitherto “non-detectable” simian virus of monkey renal cultures and raises the important question of the existence of other such viruses . . . . As shown in this report, all 3 types of Sabin’s live poliovirus vaccine, now fed to millions of persons of all ages, were contaminated with vacuolating virus.
The vacuolating virus was another name for SV40.
In 1962, Dr. Bernice Eddy published her findings in the journal produced by the Federation of American Societies for Experimental Biology. She wrote:
There is now an impressive list of oncogenic (cancer causing) viruses—the rabbit papilloma, polyoma, Rous sarcoma, the leukemia viruses . . . . It has been known for a number of years that monkeys harbor latent viruses . . . . The (SV40) virus was injected at once into 13 newborn hamsters and 10 newborn mice. Subcutaneous neoplasms indistinguishable from those induced by the rhesus monkey kidney extracts developed in 11 of the 13 hamsters between 156 and 380 days . . . .
Subsequent studies performed in the early 1960s demonstrated that SV40 caused brain tumors in animals and that SV40 could transform or turn cancerous normal human tissue in vitro. A disturbing experiment performed during this era also suggested that SV40 could cause human cancers in man in vivo. In 1964, Fred Jensen and his colleagues took tissue from patients who were terminally ill with cancer. They exposed the tissue to SV40 and then after it was transformed, they implanted the tissue back into the patient. These implants grew into tumors in their human hosts. This suggested the possibility that SV40 could cause cancers in man.
New Regulations are Implemented
By 1960, the Salk injectable polio vaccine (IPV) had been administered to about 98 million American children and adults, and Sabin’s OPV had been administered to about 10,000 Americans and millions in the USSR where the clinical trials had been conducted. It was estimated that 10% to 30% of the vaccines contained live SV40. The federal agency in charge of vaccine licensing and safety at the time was the Division of Biologics Standards (DBS) of the National Institute of Health (NIH). Incredibly, this agency did not order a recall of any of the SV40-contaminated vaccines. The tainted vaccines continued to be administered until 1963 when they were all used and replaced by allegedly SV40-free vaccines as required by the new federal regulations promulgated in 1961.
On March 25, 1961, the federal regulations that controlled the production of oral poliovirus vaccine were amended. These new regulations did not require the vaccine manufacturers to discard their SV40-contaminated poliovirus seeds which were the source for all subsequent polio vaccines. Instead, the rules required that “[e]ach seed virus used in manufacture shall be demonstrated to be free of extraneous microbial agents.” The new regulations also required that each pair of monkey kidneys removed from a monkey for vaccine production “shall be examined microscopically for evidence of cell degeneration.” Furthermore, fluid from the monkey kidney cells had to be combined with other tissue cultures in order to detect if there was any contaminating virus. The regulations required that “[t]he cultures shall be observed for at least 14 days.”
In essence these regulations required an SV40 test that was comprised of taking the monkey kidney cells upon which the vaccine would be grown and: 1) Looking at them through a microscope to see if they demonstrated SV40; 2) Taking fluids from them; 3) Introducing those fluids into other cell cultures; 4) Waiting 14 days; and 5) Seeing whether the other cell cultures were changed as a result of the presence of SV40. These tests were not designed to detect the contaminating viruses themselves. One cannot see SV40 or any virus with a standard light microscope or the naked eye. Instead, the government’s SV40 test relied on the observation of the presumed effect of an SV40 infection on certain tissue cells to demonstrate the presence of the virus.
On November 8, 1961, after the new regulations were in force, an internal Lederle Laboratories memo stated that three lots of OPV that had been released for clinical trials were probably contaminated with SV40. The memo states, “The decision by Dr. Murray to allow SV40 to be present at the PCB-2 level was the basis for our allowing these lots to pass.” The PCB-2 level comprised one set of fluids taken from the monkey kidney cells and introduced into other cell cultures to detect SV40. It was used to perform the 14-day observation tests for the presence of SV40 and had indicated that these particular polio harvests were SV40 contaminated. “Dr. Murray” referred to above is Dr. Roderick Murray who was the director of the Division of Biologics Standards (DBS) of the National Institute of Health (NIH) from 1955 to 1972. It is unknown why, according to this internal memorandum, the DBS would allow polio vaccines to be released when the very tests designed to find SV40 produced positive results of SV40 infection.
A. The Scientific Rationale for the New Regulations
In 1962, an article received for publication on September 29, 1961, appeared in the Journal of Immunology; entitled, Studies on Simian Virus 40, it was written by scientists from the DBS of the NIH. This article presented the rationale for the new SV40 safety regulations that would remain in place, ostensibly unchanged, for the next four decades. The article’s lead author was Harry M. Meyer, Jr. Dr. Meyer would succeed Dr. Murray as the director of the DBS and would hold this post from 1972 to 1987.
This article discussed some of the challenges with SV40 and polio vaccine production including the fact that the time required for SV40 to show itself in tissue culture tests was “directly related” to the amount of SV40 present. In other words, the testing required by the federal regulations for SV40 detection was dependent on the amount of SV40 present.
The authors also pointed out that it could take up to thirty-five days for SV40 detection when the virus was removed from the blood of an infected monkey. Interestingly, however, the authors also stated that it took only eleven days for low doses of SV40 to be detected when it was removed from monkey kidney cells. This was reportedly based on a single experiment. The eleven-day result was significant because the regulations only required fourteen days of observation. If low doses of SV40 could be detected in eleven days then the fourteen-day observation period would be sufficient. A close reading of this article, however, reveals that this crucial study was at best incomplete.
B. A Critique of the Scientific Basis of the New Regulations
The authors of the Journal of Immunology article stated that 10 to 100 TCID50 or “Tissue Culture Infective Dose” of SV40 was detected in eleven days. TCID50 is defined as that dilution of virus required to infect 50% of a given batch of inoculated cell cultures. Therefore, a titer of 10 to 100 TCID50 represents a substantial amount of SV40 because one-half of the cells are infected. In other words, if it took a certain sized dose to infect 50% of the cells in eleven days, it would probably take a substantially smaller dose to infect 1% of the cells in the same period. This smaller dose would then take longer to infect 50% of the cell cultures. Therefore, this article left out the important fact that very low doses of SV40 would most likely not be detected in eleven days.
Second, the government scientists used pure SV40 as a surrogate for SV40-contaminated monkey kidney cells. There is no study that demonstrates the validity of this. During vaccine production, polio seed virus is inoculated into monkey kidney cells in order to grow the vaccine. Samples of these cells are set aside and fluids are drawn off and injected into other cell cultures to test for the presence of SV40. Since these fluids are drawn from monkey kidney cells, they contain a variety of viruses, cellular components, growth medium, and other debris. The sensitivity of the SV40 test for detection of SV40 from this amalgam was the important public health question. The Division of Biologics Standards, however, did not perform this test, or if they did, they did not report their findings. Instead, they used pure SV40 without any other ingredients to determine that eleven days was sufficient.
This flaw in the methodology was demonstrated when the authors discussed the fact that after three weeks of observation, SV40 did not appear from the kidneys of four monkeys that were known to carry SV40 antibodies in their blood. The government scientists stated, “[T]he failure to demonstrate virus in the renal tissue of an appreciable number of rhesus monkeys that had been infected some time earlier was of interest.” This is an admission that even after three weeks of observation (one week longer than the federally mandated two-week observation period) the SV40 from the kidneys of SV40 contaminated monkeys (not pure SV40) did not reveal itself in culture. Unfortunately, the government scientists did not act on this important observation other than to note that it “was of interest.”
Third, the eleven-day finding was apparently based on a single experiment. There is no mention of it being repeated to ensure the accuracy of the results as required by the scientific method.
By 1965, it was well established in the scientific literature that there were several problems with the SV40 tests mandated by the Code of Federal Regulations. First, the fourteen-day SV40 tests were not long enough to detect the virus. In fact, numerous experiments by leading virologists (all non-governmental scientists) found that it took from two to five weeks for the detection of low doses of SV40. Second, there were more sophisticated microbiological tools available that could detect SV40 with greater accuracy. These tests were all widely used and accepted virological techniques. Third, there were several more sophisticated measures available to eliminate SV40 from cultures used to make the poliovirus vaccine. Nonetheless, despite the mounting scientific evidence that the SV40 tests were crude and unreliable, the regulations were not changed and oral polio vaccine manufacturers did not voluntarily adopt any technical improvements to ensure that SV40 was detected and eliminated from their products.
The Flawed Epidemiology
After SV40 was originally detected in the Salk and Sabin vaccines that had been administered to millions of children around the world, the scientific community held its breath and wondered if these children would be stricken with cancer. Indeed, the pediatric cancer rate continued to climb through the 1960’s, 70’s, 80’s and 90’s. But, the few epidemiological studies that looked for a direct link between SV40 and human cancer provided inconsistent conclusions. Some reports found that there was an increased risk of cancer from SV40 exposure and others found that there was no risk. Each of these studies suffered from major flaws including the fact that no one knew who actually received the SV40-contaminated vaccines and who did not, so it was impossible to compare an SV40-exposed group with a non-exposed group.
SV40—A Human Carcinogen
By 1999, numerous pathologists, microbiologists, and virologists throughout the world had detected SV40 in a variety of human cancers such as brain tumors including medulloblastomas, bone cancers, and mesotheliomas a fatal lung cancer. These were the very same cancers that were created when SV40 was introduced into animals. The advent of Polymerase Chain Reaction (PCR) technology that could identify the genetic code of specific strands of DNA demonstrated with precision that it was this monkey virus that was being detected in human cancers and no other. Moreover, the rates of these particular cancers had steadily increased over the last few decades. The question that had been left unanswered for almost four decades now faced scientists again—was SV40 responsible for causing or contributing to human cancers?
Over the last forty years since its discovery, SV40 had become one of the most widely studied and best understood viruses in microbiology. It was routinely used to create human cancers in the laboratory in order to test cancer therapies. In addition, it is now known how this virus caused cancer on a molecular level. After careful study documented in peer reviewed publications, leaders in SV40 research announced that SV40 was a class 2A human carcinogen.
The Government’s Response
Nonetheless, the various United States government agencies such as the Centers for Disease Control (CDC) and National Cancer Institute (NCI) disputed these conclusions. According to the CDC, “SV40 virus has been found in certain types of cancer in humans, but it has not been determined that SV40 causes these cancers.”According to the National Intsitutes of Health (NIH), “the NCI is continuing to evaluate the possible link between SV40 infection and human cancers.” A question has been raised whether this continuing evaluation is being performed with complete scientific integrity. One article written by an attorney and published in a peer reviewed scientific journal describes how the NCI deliberately compromised a study that would have demonstrated the association between SV40 and mesothelioma.
While the United States government continues to evaluate whether or not SV40 represents a public health threat and whether SV40 is a human carcinogen, several scientists at the NCI concluded that SV40 contributed to the formation of mesotheliomas. In fact, the federal government has licensed technology to target SV40 in the treatment of human mesotheliomas.
SV40 and the Public Health
Despite the government’s foot dragging, in the last several years, scientists from around the world have made startling and disturbing discoveries. They have found SV40 antibodies in a significant percentage of people including children who were too young to receive the SV40 contaminated vaccines of the early 1960’s. They have also discovered that cancers with SV40 are less likely to be responsive to chemotherapy and radiation because SV40 interferes with the genes necessary for cancer cells to die when they are exposed to chemo or radiation therapy.
The Institute of Medicine Report
In July 2002, the National Academy of Science Institute of Medicine (IOM) Immunization Safety Committee convened a study into SV40 and cancer which culminated in a report published in October 2002. According to the IOM report “SV40 Contamination of Polio Vaccine and Cancer”:
The committee concludes that the biological evidence is strong that SV40 is a transforming [i.e., cancer-causing] virus, . . . that the biological evidence is of moderate strength that SV40 exposure could lead to cancer in humans under natural conditions, [and] that the biological evidence is of moderate strength that SV40 exposure from the polio vaccine is related to SV40 infection in humans.
Source: sv40foundation.org
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