sjmcmahon

> There are researchers that claim this makes it an even more virile cancer causing agent.

This is exceedingly vague, but also seems to fall into "extraordinary claims" territory.

We know the proteins SV40 expresses that immortalise cells, and we know their targets. Moreover, we know that delivering the proteins independently of SV40 can still immortalise cells, but SV40 mutated to disable those proteins can't.

The claim that the promoter by itself is a stronger cancer causing agent requires it to have an entirely different mechanism of action, but also one which isn't activated by all the other ways DNA fragments containing promoters can get into cells - like, say, everyday viruses. At first glance it doesn't pass the sniff test.

Not the GP poster, but some answers:

> Does SV40 cause cancer?

Yes, in a range of animal models at least.

SV40 can 'immortalise' cells, turning off regulatory functions which prevent uncontrolled division, which is an important part of carcinogenesis. This has been shown to contribute to cancer in experimental systems.

> Did and does SV40 inadvertendly inside the Polio Vaccine in the late 1950ies and 60ies cause cancer?

The evidence suggests not significantly, although it's impossible to rule out for some unlucky individuals.

The SV40-exposed cohorts rates of cancers don't differ that greatly from unexposed groups, so we can say with certainty that the rate is much less in humans than seen in laboratory systems. There were suggestions of differences for some cancers, but these are heterogeneous and often confounded, and the general consensus now seems to be the effect was small if not zero. I don't think there's a definitive answer on why - possibly the exposure was sufficiently low or the virus was not effective at infecting humans to significantly affect the carcinogenic processes.

> Does the Pfizer proces 2 SV40 promotor in the Covid Vaccine cause cancer?

Certainly not by the mechanism intact SV40 causes cancer.

That depends on the production of particular SV40 proteins which interfere with cell functions, which aren't present in that promoter.

> Does DNA contamination in general cause cancer?

In general, no.

Cells are constantly exposed to both native and foreign DNA fragments, and have plenty of mechanisms for dealing with them. Even if fragments were somehow incorporated and expressed, most are not inherently carcinogenic.

Setting aside my bias about whether my large glass of wine last night was one drink or two, I find the claims in this post odd. None of the issues noted seem inherently problematic, and indeed several are as I would expect. Disclaimer: not an epidemiologist, although I do fit models to data and have seen more than a few epidemiology talks.

1: Asymmetric CIs aren't mysterious. Any parameter fit to anything beyond the simplest model and data will have asymmetric CIs. We often neglect this and assume a symmetric (normal) approximation, but in complex data you really should calculate the proper CIs.

2: The data in the age groups wouldn't be expected to be either fully dependent or independent. Looking at the data and assumptions that goes in, some affects all age groups, some only one, and there's model effects between groups (if you die due to alcohol at 30, you can't also die due to alcohol at 50). The CI size lying somewhere between independent and fully correlated is exactly what you'd expect there.

3. The last complaint is a more fair, but also common: most people who die are old, and most causes of death go up when you get old, so CIs get big when you have to subtract large numbers. More data is always welcome there, but also famously hard to get.

So, none of these seem like show stoppers to me, and the way some of them are presented in the post ("mysterious asymmetric CIs") seems to speak to a motivation to knock this study down.

I agree the stats methods in the paper are a bit thin, but I'm not sure how much of that is standard practice in the field. But I think that's a case for asking more detail, rather than denying the results out of hand.

Most radiobiological effects for acute exposures are actually quadratic in dose - this applies to things like mutations, chromosome aberrations, and lethal events.

The quadratic term relates (loosely) to interactions between damage from multiple ionising particles which are present in cells at the same time. When you protract exposures, more damage is repaired before subsequent ionising particles arrive, and you see a reduction in the quadratic term, to effectively a linear form at very low dose rates.

So it's not surprising that spreading the radiation out significantly reduces the yield of biological events, but actually supports a linear trend for mutation yield in low-dose and low dose-rate conditions. (Whether that tracks linearly in turn to cancer risk, on the other hand, is a topic of much more debate.)

The article is a bit unclear, but we have both a very wide range of X-ray vs charged particle studies, and increasingly of conventional vs FLASH studies with a range of modalities (e.g. the seminal FLASH paper was FLASH electrons vs conventional electrons). FLASH photon vs conventional photons are also increasingly being generated, although they've been more of a pain to generate.

So it's clear there is a temporal FLASH effect, which is not purely a question of radiation type.

That's not to say it's necessarily exactly the same effect - we still don't have a perfect quantitative understanding of the effects of different radiation types even at normal dose rates, let alone when FLASH differences are added into the mix.

That phrasing isn't perfectly clear, as there's two things at play.

If you're delivering a large dose D all at once, FLASH spares normal tissue compared to conventional rate irradiations, with maintained anti-tumour effect.

But, you can instead deliver your treatment in a number of smaller doses, say n "fractions" of dose d. This also spares normal tissue (1). This latter approach - fractionation - is the way radiotherapy was delivered for most of its history. But at these low doses, FLASH sparing is small to negligible.

So, we have two demands in tension - and its unclear which is actually optimal. Some of the early results in FLASH showed huge sparing, but lots of more recent studies have shown more modest effects which may not be worth giving up benefits of fractionation for(2). And to date I think we have basically no meaningful in-human data to guide this, so there's still a lot of uncertainty.

1 - Fractionation also spares tumours, a bit, but you can offset this by increasing the total dose a bit and still see benefit.

2 - There is a general move to somewhat larger, fewer fractions even in normal radiotherapy, although almost all of these are still below the threshold where FLASH sparing is seen.

This is generally good advice, but isn't it inappropriate in this specific instance?

The lady's claim was (allegedly) that she has a perfect ability to distinguish between the tea-milk orders, so in that case even a single failure is indeed enough to reject her claim.

We can't rule out her success rate being significantly greater than 50-50, but even a single failure puts some bounds on her maximum success rate.