Introduction

Lately, there has been a little more buzz than usual about SV40. Simian (i.e. monkey) virus 40, a DNA tumor virus, is believed to have been introduced to a significant portion of the human population between 1955 and 1963 through polio vaccines. The polio vaccines were prepared in the kidney cells of rhesus monkeys, and apparently were contaminated with SV40 present in those cells.

On August 29, the NCI published a study entitled, "Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos cocarcinogenicity." Anytime SV40, asbestos and mesothelioma are mentioned on the same page, asbestos plaintiffs' attorneys, and especially defense attorneys, are going to sit up and take notice. Based on studies that as much as 60% of human malignant mesothelioma contains SV40 DNA, asbestos defense attorneys have been hunting for proof that SV40, and not asbestos, causes mesothelioma. Statements from the study like, "We found that human mesothelia are uniquely susceptible to SV40," might suggest that the study offers such proof.

My view however, is that the study will have little or no affect on mesothelioma litigation. But with some good will, good fortune, and good science, it may lead directly or indirectly to greater treatment options for mesothelioma patients.

Summary of the SV40

Asbestos Cocarcinogenity Study According to the study, mesothelial cells are much more susceptible than other human cells to transformance, i.e., the malignant process of abnormal and continuous cell reproduction, by SV40. In non-mesothelial tissue, SV40 replicates actively, quickly leading to cell death. But apparently, the elevated levels of the protein p53 in mesothelial tissue, as opposed to other human tissue, inhibit SV40 replication, thereby limiting cell death. As a result, since the cells are not simply killed, transformance can occur.

Further, the study reports that SV40 appears to act synergistically with asbestos to transform mesothelial cells, thus indicating that SV40 and asbestos may be cocarcinogens. The report's conclusion, in its own words, is that "Malignant mesothelioma may be a new example of cocarcinogenesis between a virus (SV40) and a ubiquitous environmental carcinogen (asbestos)."

The article does not overturn more than 50 years of published research proving that asbestos causes mesothelioma in humans. Beginning simply with the premise that in tissue culture, i.e., in vitro, asbestos does not "transform" mesothelial cells, the study seeks to explain how transformance of mesothelial cells might occur in vitro. "The role of asbestos in causing malignant mesothelioma has been firmly established epidemiologically; however, it has been difficult to reconcile the epidemiological findings with the inability of asbestos to transform mesothelial cells in tissue culture."

Arguing that science does not yet understand the precise mechanism by which asbestos causes mesothelioma does not undermine the established proof that asbestos fibers cause mesothelioma. This was the same argument the tobacco lawyers made for years -- "since we don't know the exact mechanism by which tobacco smoke turns healthy lung cells into malignant cells, we can't say that smoking causes cancer." This argument has been rejected as fallacious, both by scientists, and by juries.

To shed light on how transformance does occur in human mesothelioma, the study examines the effects of the SV40 contaminant and asbestos on mesothelial cells in petri dishes. It indicates that, again in vitro, SV40 is able to cause some mesothelial cell transformance, and that tissue culture exposed to both SV40 and asbestos results in much more transformation. Thus the study concludes that SV40 may be a cocarcinogen, with asbestos, in causing mesothelioma. This does not prove that SV40 alone causes mesothelioma. Nor does it eliminate asbestos as a cause of malignant mesothelial cell transformation. On the contrary, it shows that in vitro, asbestos combined with SV40 does cause transformance, significantly more than does SV40 alone.

Furthermore, the study recognizes that the way asbestos operates in isolated mesothelial cell culture in vitro does not fully describe the way it operates on actual human tissue, in vivo. In the human body, "asbestos induces the production of oxygen radicals by macrophages, which may promote gene alterations and carcinogenesis. Thus it is possible that in vivo, asbestos has stronger effects on carcinogenesis than in vitro." Far from proving that asbestos does not cause mesothelioma, the study recognizes that in the human body, asbestos may be even more carcinogenic than it is in the confines of a petri dish.

The Study's Effect in the Courtroom

While the study may be helpful in identifying one way that asbestos might operate with SV40 or other factors to cause mesothelioma, it does not prove that SV40 is the only thing which causes mesothelioma, or even is essential in causing it. Aside from SV40, there are a myriad of human DNA viruses, and one or more of these may be similar to SV40 and act with asbestos in vivo the same way SV40 does in vitro.

Indeed, the evidence is that SV40 cannot be necessary to cause mesothelioma. Many cases of mesothelioma have been diagnosed in individuals who were not exposed to SV40. For example, mesothelioma occurs in Finland and Turkey, yet neither country received contaminated polio vaccines. In fact, SV40 is not present in mesotheliomas from Finnish or Turkish patients.

Further, researchers were reporting mesothelioma cases in the literature as far back as the early 1900s (Robertson in 1923 and Klemperer and Rabin in 1930). And the association between asbestos and mesothelioma found its way into the published literature in the 1940s -- a decade before the first infected polio vaccines were given anywhere.

Finally, the study itself quantifies the proportion of malignant mesothelioma containing SV40 DNA as about 60%. It therefore follows that in at least 40% of the cases, a human who did not carry the virus nevertheless developed mesothelioma. All these facts indicate that SV40 is not a necessary pre-condition in causing mesothelioma.

My view therefore is that in the courtroom the study will not alter 50 plus years of scientific evidence that asbestos "causes" mesothelioma.

The Study's Effect on the Search for Treatments - Possible Hope for Mesothelioma Victims

Lawyers for plaintiffs and defendants can disagree on the cause or causes of mesothelioma. But there is one thing we should agree on: Basic research on the mechanism by which tumors are caused at the genetic level provides a foundation for applied research on developing treatments for this "uncured" cancer. (I say "uncured" because it is dishonest to call mesothelioma "incurable" without ever truly committing to try to cure it.) Millions of dollars have been burned up on courtroom experts. I hope that both sides, and their lawyers, will think outside the box and support any research that can expand treatment options for mesothelioma patients.

The SV40 - Asbestos study offers hope in this regard. It suggests that one way mesothelioma may develop is through viral antigens which act in concert with asbestos. It may be possible for scientists to target the viral antigen with a viral protein in the form of a vaccine. The study further suggests that select proteins (p53 in the case of SV40) may actually limit the cell death which a particular viral antigen would otherwise cause, allowing the cell, in the presence of asbestos to transform malignantly. This offers hope that genes could be engineered to act on the mesothelioma cell's DNA and "turn off" those select proteins that keep the cancer cell alive and reproducing. Finally, if indeed the presence of the SV40 infection "may negatively influence prognosis" as the article posits, then at the very least we should be working on finding new tumor markers to test for early stage mesothelioma -- or even genetic susceptibility to this cancer -- in those persons who have known exposures to asbestos.

The existence of these possibilities, if it were coupled with the collective will to fund the research necessary to develop them, would offer real hope to mesothelioma victims.

Roger G. Worthington