Document xy7RmeGr4jy38xxM572yqG9b

F. H. Schroder (Department of Urology), Erasmus University, Rotterdam, The Netherlands. Correspondence to: Robert F. Hoedemaeker, M .0,, Department of Pathology, Erasmus Univer sity, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands (e-mail: Hoedemaeker path.fgg. eur.nl). Re: Debate on the Link Between SV40 and Human Cancer Continues The news article by Nancy J. Nelson {}) repeats the current scientific dogma that simian virus 40 (SV40) was re moved from all oral polio vaccine sold and administered in the United States, In a recent article (2), however, I have challenged this accepted "fact" based on legal documents and the absence of test results from at least one of the principal vaccine manufacturers, Lederle. As noted in that article, internal Lederle documents indicate that the company has not been able to document that it tested all vaccine seeds to confirm the absence of SV40 contamination. There fore, statements in Nelson's article, such as "[pjeople most likely to have re ceived contaminated vaccines were bom from 1941 through 1961," are inaccurate and potentially misleading. Dr, Stickler's statement that "[m]esotheliomas are developing in people who are too old to be vaccinated, and brain tumors [are developing] in chil dren that are too young to have been vaccinated," may be explained by the presence of SV4Q in the oral polio vac cine and the fact that oral polio vaccine can spread from the recipient to those who come in contact with the excretions (oral and fecal) of the recipient within a defined period of time (J). There has been no investigation of whether SV40 can be transmitted from individuals vac cinated with the live oral polio vaccine to unvaccinated individuals because ev eryone has assumed that SV40 was never in that product from the inception of its being sold in the United States. Every scientist who is attempting to determine the role of SV40 as a cause of cancer in humans and every news re porter who is interested in this issue should demand all of the records of both the government and the vaccine manu facturer so that there can be a full sci entific and independent investigation as to whether there was full compliance with the removal of 5V40 from all oral polio vaccine used in' the United States from 1962 until 2000. Oral polio vac cine is no longer sold in the United States, and only enhanced inactivated vaccine is now allowed for routine im munization. Stanley P. Kops References (1) Ndson NJ. Debate on the link between SV40 and human cancer continues. J Natl Cancer Jnst 2001',93:1284-6. (2) Kops SP. Oral polio vaccine and human can cer: a reassessment of SV40 as a contaminant based upon legal documents. Anticancer Res 2000:20:4745-9. (3) Henderson DA, Witte JJ, Morris L. Langmuir AD. Paralytic disease associated with oral po . Iso vaccines, JAMA 1964;190:41-8. Notes . Correspondence to: Stanley P. Kops, Esq., 210 West Washington Square, Third Floor, Philadel phia, PA 19106 (e-mail: stankops@aol.com). Overall, Nancy Nelson's news article about simian virus 40 (SV40) and hu man tumors (?) was well balanced. We would like to make some additional comments. (More information can be found in the February 2001 issue of Seminars in Cancer Biology.) First, the statement in the sidebar that SV40 causes "abnormalities" jn human cells underestimates the extent of dam age. Human cells infected by SV40 in vitro develop extensive genetic damage [(2), reviewed in (3)] and have grown as tumor nodules when injected into volun teers (4). The susceptibility of human cells to SV40 is cell type dependent, with mesothelial cells the most suscep tible (2,3,5). SV40 is the only known carcinogen that, by itself, causes malig nant transfoimation and immortalization of human mesothelial cells in tissue cul ture (2,3,5). Second, the incidence of mesothelio ma in the United States has increased from nearly none in 1955 to approxi mately 2500 cases per year, and SV40 may be one of the contributing factors. Third, the hypothesis that most me sotheliomas occurred in an age group that could not have been exposed to SV40-contaminated polio vaccines (J) reflects a common but mistaken belief that, during the "contamination" period (1955 through 1961), only newborns and children were vaccinated. In the United States, 34,7 million people aged 20-59 years were vaccinated with po tentially contaminated polio vaccine during this period (3). This is the cohort in which most mesqjheliomas have de veloped in the past 20 years (3). Further more, administration of the oralattenuated polio vaccine in the early 1960$ exposed both the recipient and his contacts to the poliovirus and to SV40 because both viruses were infectious. There is also evidence that SV40contaminated vaccines were produced and distributed after 1961 (6). Finally, even if polio vaccines contributed to the spread of SV40, other mechanisms of transmission presumably exist because SV40 has been detected in nonvaccinated individuals (3). Fourth, epidemiology studies [re viewed in (3)] have measured the asso ciation of the polio vaccine with the overall increase in cancer. However, one would not expect increases in rare can cers such as mesotheliomas to affect overall cancer rates. Two independent studies of cohorts vaccinated in early childhood with potentially contaminated polio vaccines (3) suggested an in creased risk of mesothelioma (relative risk, s*3). However, the number of cases was small because mesotheliomas are rare in people younger than 50 years; thus, it is premature to make definitive conclusions about an increased risk of mesothelioma in individuals vaccinated with SV40-contaminated polio vaccines (3). Fifth, several groups have used vari ous technical approaches (immunostaining, messenger RNA in situ hybridiza tion, and primed in situ hybridization) to demonstrate that SV40 is present in ma lignant mesothelioma cells but not in nearby normal cells (3). Moreover, SV40 has been detected in mesothelio ma cells and not in nearby nonmalignant cells microdissected from the same slide (5). Sixth, SV40 is not always lost when mesothelioma cells are cultured (5)-. ac- j cordingly, treatment with an antisense i construct to the SV40 T antigen arrests S V40-positive mesothelioma cells in tis sue culture [reviewed in (7J]. Also, Epstein-Barr, another episomal virus, is of ten lost when human nasopharyngeal tumor cells are put in tissue culture. Seventh, it has recently been shown that a small number of mesothelioma Journal of the National Cancer Institute, Vol. 94, No, 3, February 6, 2002 CORRESPONDENCE 229 NOTICE: bv THIS MATERIAL 'yi .vs* ft,iay ee protected cells infected with SV40 can induce the growth of nearby noninfected cells (5). Eighth, enzyme-linked immunosor bent assay tests are not reliable to dis tinguish among SV40 and the human polyomaviruses JC and BK. However, DNA sequencing can reliably distin guish these three viruses (3). Finally, experts from around the world in the fields of virology, molecu lar genetics, mesothelioma, brain and bone tumors, and oncology, including many skeptical of the association be tween SV40 and human cancer, dis cussed it at a consensus meeting at the University of Chicago, IL, on April 20 21,2001. The scientists who chaired the final panel discussion (and who are not directly involved with this research) concluded that "the presence of SV40 in some human tumors has been convinc ingly demonstrated ... the possible role of SV4Q in the pathogenesis of mesothe lioma has been considerably strength ened since the 1997 NCI conference" (7). ' References Michele Carbone Harvey I. Pass (!) Nelson NJ. Debate on the link between SV40 and human cancer continues. J Natl Cancer Inst 2001;93:1284-6. (2) Boccheua M, Di Rests I, Powers A, Fresco R, Testa JR, Pass HI, et a). Human mesotheliai ceils are unusually susceptible to SV40 medi ated transformation and asbestos co-carcino genicity. Proc Natl Acad Sci U S A 2000-.97: 10214-9. (3) Carbone M, Kratzke RA, Testa JR. The patho genesis of mesothelioma. Semin Oncol. In press 2002. (4) Jensen F, Koprowski H, Pagano JS, Ponten J, Ravdin RC. Autologous and homologous im plantation of human cells transfoimed in vitro by SV40. J Natl Cancer Inst 1964;32:917-32. (5) Cacciotti, P. Liberier R, Bella P, Martini F, j Porta C, Procopio A, et al, SV40 replication in human mesotheliai cells induces HGF/Mei re ceptor activation: a model for viral-related car cinogenesis of human malignant mesothelio ma. Proc Natl Acad Sci U S A 2001 ;98: : 12032-7. (<5) Kbps SP. Orel polio vaccine and human can cer. a reassessment of SV40 as a contaminant based upon legal documents. Anticancer Res 2000;20:4745-9. (7) Klein G, Powers A, Croce C. SV40 and hu man tumors. Oncogene. In press 2001. Notes Affiliations of author?.- M. Carbone, Cardinal Bemardin Cancer Center, Loyola University i Medical School Chicago, Maywood IL; H. I. Pass, Kermanos Cancer Institute, Wayne State Univer sity, Detroit, ML Correspondence to; Michele Carbone, M.D., Ph.D., Cardinal Bemardin Cancer Center Room 205, Loyola University Medical School Chicago, 2160 S. Fust Ave., Run. 205, Maywood, IL 60153 (e-mail: mcarbon dtorion.it.luc.edu). 230 CORRESPONDENCE Journal of the National Cancer Institute, Vol. 94, No. 3, February 6, 2002