The undead undead-- Virus myths that wont die: SV40

There are lots of controversies in viral research.

Not just woo ones, like whether HIV-1 exists and causes AIDS, but real controversies that have been going on for some time, like whether HIV-1 infects dendritic cells or DCs just carry-->pass on virions.

The public hears about the stupid stuff, but dont know (dont care?) about the real controversies. This travesty has a third negative effect, in that sometimes the public never hears the resolution to the stupid stuff, thus it lives on in word-of-mouth whispers and the internets underbelly, long after science has soundly whooped the stupid claim.

I was reminded of an oldie but goodie-- a perfect example of how completely normal and reasonable science can be twisted into woo by stupid or manipulative people from an article on XMRV. Apparently, XMRV is not just latching on to Chronic Lyme woo, but also SV40.

SV40! Talk about a blast from the past!

SV40 is old-school-- Discovered in 1960. It, like many viruses, became a priceless laboratory tool for understanding biology-- specifically cell biology/tumor biology. Bad-news-bears popped up when it was discovered that the cell line used to make the polio vaccine also produced SV40, and though SV40 is harmless in its natural hosts (monkeys), if you pumped it into hamsters, they got tumors.

Well, crap.

There was no evidence at the time that any human was harmed from the vaccines, but its not exactly a bell-and-whistle that needs to be there. We screen human vaccines for wayward RNA/DNA/RT activity/etc today, but that was not possible back in the 1950s when this vaccine was produced. So, it was one of those 'we lucked out, and we learned something' mistakes.

... But then a lab found SV40 in particular kinds of human cancer.

warblegarble.

Multiple lines of evidence, from antibodies to SV40 to PCR. And unlike a current controversy in virology, the SV40 researchers actually had a plausible biochemical mechanism for how/why SV40 was causing this disease. It was starting to look pretty bad. So the NCI set up a SV40 working group in 1997:

In order to resolve why some laboratories detect traces of SV40 in mesothelioma while others do not, an International SV40 Working Group, which included the majority of laboratories studying SV40 in human tissues, was formed in 1997. Nine laboratories from the working group agreed to participate in a study, funded and organized by the National Cancer Institute (NCI). Each group was given 25 paired-duplicate samples of human mesotheliomas, a single set of 25 normal lung tissue samples, and positive and negative control samples. All the samples were blinded (labeled so that the human tumors and controls could not be distinguished) and each laboratory used its particular assay for detecting SV40, many of which had been used to detect SV40 previously. The results, published in the May 2001 issue of Cancer Epidemiology, Biomarkers and Prevention (36), showed that none of the mesothelioma specimens was consistently positive for SV40.

Sounds familiar. Some labs can find SV40, some cant, and the ones that can find it, cant do it reproducibly.

Furthermore, the epidemiology of SV40-->cancer does not make sense. Cancer rates did not go up in populations exposed to the polio vaccine (in fact, sometimes they went down). Elderly, adults, children-- no group shows an increase in cancer incidence based on putative exposure to SV40. Scientists even looked at populations in Northern India (where SV40 is out in the wild monkey population, thus humans might be exposed to it 'naturally' there), and there was no association between cancer and SV40.

Scientists have even looked for antibodies to SV40 in the general population (those things Judy Mikovits thinks 'proves' she is correct? "We identified a human antibody response... These scientific findings cannot be explained by contamination..."). The anti-SV40 antibodies scientists found... were not actually specific for SV40. They cross-reacted with BK virus (a totally normal virus that we have all been infected with at some point that you dont even notice). When they used a super-specific test, there was no difference between cancer/healthy people.

This controversy has been going on for about 50 years. It finally became the scientific consensus in 2004 that SV40, even if it was a viable contaminant in polio vaccines, is not associated with any human cancers.

But here it is, 2011, and there are still papers that have to put in their abstracts "Simian virus-40 (SV40) is a DNA tumour virus that was introduced into the human population with contaminated poliovirus vaccine, and its role in mesothelioma is widely debated" and "Malignant mesothelioma is predominantly caused by asbestos exposure, although the association of Simian virus 40 in its pathogenesis is currently still under debate." even though their conclusions are "Using this sensitive and specific detection method, we were unable to identify SV40 miRNA expression in human malignant pleural mesothelioma (MM) samples." and "We found no evidence of SV40 presence in tissue samples from 103 Slovenian patients with malignant pleural mesothelioma."

2011, and you can still go to the websites of any of The Usual Suspects, and hear sob stories from 'patients' who are XMRV positive AND Lyme positive AND SV40 positive, and all this must have caused their childs autism/cancer/etc... Google 'SV40' and crank sites out-rank the National Cancer Institute.

*sigh*

The undead undead dont die easily, apparently...

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Hm. Brings new meaning to the phrase 'zombie virus'. I will never be able to understand why the obviously wrong target is better than not knowing what/who to target.

"Sounds familiar. Some labs can find SV40, some cant, and the ones that can find it, cant do it reproducibly."

So in the case of labs that did "find" SV40, was this a case of contamination of samples, nonspecific primers, or something else (or not determined)?

By Poodle Stomper (not verified) on 16 Feb 2011 #permalink

I have read your posts on XMRV, the PCR test, and "Mikovits' character". Those provided me with arguments when debating XMRV with fellow patients, but I had no arguments against the serology test. The serology test was used to downplay the importance of the (PCR) contamination papers in Retrovirology. Until I was alerted to an article on a German site (original article: http://www.faz.net/s/Rub7F74ED2FDF2B439794CC2D664921E7FF/Doc~EDC81ADBEF… )
Google translation of quote:

With all the negative European studies were reliable detection methods have come on the basis of antibodies used, says Joachim Denner. The Berlin virologist was himself involved in some of the tests and know from long experience to potential sources of error. Even with proven non-infected people could sometimes detect antibodies to individual HIV proteins. To those non-specific antibodies are not to misread as evidence of infection, the tested blood samples in the HIV testing should always be against more than one viral protein judge. On such vital controls are lacking not only in the publication of Mikovits.

I was going to write to you about this, but if I understand correctly by now, you just don't test for antibodies, but you have to test for specific antibodies and that this kind of information/research/consensus is still lacking for XMRV.

How does this process work, for lets say HIV or SV40? A process of elimination, all the non-specific antibodies out, and then a consensus on which of the specific antibodies to use in a test?

phage-- I know, right?

Stomper-- Yes :)

Johan-- I could walk into a local clinic, right now, take the quick HIV-1 test (looks for secreted antibodies to HIV), and test positive. Right now, my allergies are gearing up REAL good, so I might, by chance, be making an 'anti-HIV' antibody, even though I am not infected with HIV.

This randomness is how your immune system works. By chance, you have antibodies that *kinda* recognize everything from HIV to SARS to microscopic space monkeys. Its only when you are actually infected with these pathogens that you make REALLY GOOD antibodies.

So, say I test positive with the quick test. The lab will then 1) look in my blood for HIV-1 proteins, 2) look in my blood for antibodies that are specific for HIV-1 proteins (3 different ways). If Im only weakly Envelope positive, and then two weeks later everything is negative, its not real.

Its especially not real if they mix my antibodies with HIV-1, and nothing is neutralized. The anti-HIV antibodies should stick to the virus and keep it from infecting cells.

No one with 'XMRV antibodies' has neutralizing antibodies.

The antibodies might recognize an XMRV-epitope, but they are not XMRV specific due to XMRV infection.

This is college/grad level immunology, so I wouldnt expect patients to know this. I would expect Mikovits to know this. *blink*

There is a lab where I go to grad school that still links SV40 to human cancers. In fact, when we had our General Virology course, it was included in the list of cancer causing viruses.

I'd heard there was a controversy, but I never really paid attention. I'll have to ask my friend who just graduated from there.

This is college/grad level immunology, so I wouldnt expect patients to know this.

Of course, if we could expect patients to know this, maybe it would keep viral woo from gaining such a persistent foothold. The reason most of these ideas continue to propagate is due to partial and/or deliberately twisted information.

"The public hears about the stupid stuff, but dont know (dont care?) about the real controversies."

Probably that most can't even comprehend the basics of the science behind it... you are talking about a group of people that shook their collective heads in agreement when BillO spouted his "tides go in, tides go out," goddidit!1!1 nonsense.
Great post, btw. Ceiling cat iz pleezed!

ERV,
You state: "2011, and you can still go to the websites of any of The Usual Suspects, and hear sob stories from 'patients' who are XMRV positive AND Lyme positive AND SV40 positive".

That is very interesting. I know where one can obtain commercial Lyme or XMRV testing. Exactly where would one go to be commercially tested for SV40?

If I read you correctly, other than the blanket population testing for cancer prevalence in the SV40 adventitious agent polio vaccinated demographic, only mesothelioma has been ruled out as a cancer connection? Not other types of tumors/cancers?

According to wikipedia, Maurice Hilleman played a role in the discovery of "the cancer-causing virus SV40".

By William Wallace (not verified) on 19 Feb 2011 #permalink