12 minutes ago, iNow said:

Perhaps if there is a valid point in your argument somewhere it's at the population level... in that we're allowing the weaker members of the herd to survive and reproduce thanks to the vaccines instead of letting them die and only allowing those naturally born strong enough to survive without vaccines to reproduce.

Thanks for trying, thinking about it, I'm not sure what we could do if studies showed a validity to my argument; which one don't we vaccinate against?

5 hours ago, iNow said:

Perhaps if there is a valid point in your argument somewhere it's at the population level... in that we're allowing the weaker members of the herd to survive and reproduce thanks to the vaccines instead of letting them die and only allowing those naturally born strong enough to survive without vaccines to reproduce.

That then goes into the other argument is that we are then limiting the gene pool again.

5 hours ago, dimreepr said:

Thanks for trying, thinking about it, I'm not sure what we could do if studies showed a validity to my argument; which one don't we vaccinate against?

Simple example that we have discussed already: malaria. While there is a vaccine now (which is only somewhat effective) in the past there was none and in malaria-rich areas the population have a higher than typical prevalence of sickle-cell genes. These of course increase the risk of sickle-cell anemia. If there was a 100% effective vaccine, their levels would be close to those in malaria-free areas.

In that scenario, would you consider you argument to be valid? And if so, how? Explain your reasoning, please.

7 hours ago, iNow said:

Perhaps if there is a valid point in your argument somewhere it's at the population level... in that we're allowing the weaker members of the herd to survive and reproduce thanks to the vaccines instead of letting them die and only allowing those naturally born strong enough to survive without vaccines to reproduce.

But having a gene to survive one malady might mean susceptibility to something else, and a gene that makes you susceptible to one could be really good protection against another, as with (or similar to) malaria.

One issue here is trying to make simplistic arguments (e.g. movie-plot threat arguments like War of the Worlds) about a complex system.

Seems to me from the discussion this comes down to dispelling the simplistic, wrong (and potentially nazi-like?) notion that there is a gene for "strength" and another for "weakness", so the "weak" should be allowed to die off. Whereas in fact it doesn't work like that, because it's a multidimensional issue, so"strength" along one axis tells you nothing about other axes.

Edited August 20Aug 20 by exchemist

Yes, similar answers from several of us on genetic diversity and multiple axes of fitness. My conjecture along one such axis would be that a lot of us do now have more robust immune systems which arose from that shift of human populations from widely dispersed to urban concentrations.* Cities, especially crossroads type cities with lots of international traffic and frequent bursts of new pathogens, were likely crucibles of intense selection that favored a fairly "multilingual" immune system.

I would say that modern times, if anything, are amplifying that selective effect, especially in teeming metropolises of developing nations where there are now both "efficient" (from the microbial perspective) global conduits for rapid introduction of exotic pathogens and higher infant/juvenile mortality. The millions living in and sometimes circulating out of crowded refugee camps also face these Darwinian pressures. This painful reality in no way argues for perpetuating such conditions, but it does suggest that we humans are continuing to have selective pressures towards fortifying "close quarters" immune systems. But it seems to me likely that rural life, especially in the third world, also offers selective pressures from the incursions of novel zoonotic pathogens.

* festering warrens in my own family tree include ports like Belfast, Odessa and Karlshamn, and a nod of thanks to these grimy petri dishes for their contributions to a pretty tough immune system.

22 minutes ago, swansont said:

But having a gene to survive one malady might mean susceptibility to something else, and a gene that makes you susceptible to one could be really good protection against another, as with (or similar to) malaria.

One issue here is trying to make simplistic arguments (e.g. movie-plot threat arguments like War of the Worlds) about a complex system.

That is exactly it. "Healthy" is actually a bit of a tricky term as we often do not really have a clearly defined optimization parameter to look at. As mentioned multiple times, there is no such things as a strong or a weak gene in isolation. And strong selection in a gene pool can leave a much less diverse gene pool that then becomes weaker to changes in selective pressures.

Likewise, even things like a strong health can be difficult to define. What if you are physically ailing, but survive for a long time? What if for some reasons you are very fertile but die young? What if you have been exposed to many infections and might have strong memory effects in your immune system, yet the repeated infections have irreparably damaged your organs?

10 hours ago, CharonY said:

...Likewise, even things like a strong health can be difficult to define. What if you are physically ailing, but survive for a long time? What if for some reasons you are very fertile but die young? What if you have been exposed to many infections and might have strong memory effects in your immune system, yet the repeated infections have irreparably damaged your organs?

Not to mention having an immune system admirably equipped to defend against infestations of intestinal worms that gets 'bored' when there are no worms to deal with.

No one wants bored intestines.

3 minutes ago, TheVat said:

No one wants bored intestines.

Would be a lot worse if they were boreless

A world of pointless pain.

6 hours ago, sethoflagos said:

Not to mention having an immune system admirably equipped to defend against infestations of intestinal worms that gets 'bored' when there are no worms to deal with.

There is potentially yet another thing at play here. In many cases, the immune system does not really fight them off. Many helminths happily reside in the gut and what many do is to modulate the immune responses of their host (many mechanisms have only recently been discovered). The overall result is that immune-related ejection is suppressed which incidentally also reduces the likelihood of allergic reactions. I think based on the molecular knowledge we have now, we can move away from the original rough hygiene hypothesis and dig a bit deeper into mechanisms.

The bottom line is that the immune system is an incredibly complex system which many interactions between the body and its inhabitants. It is almost impossible to define a "best" state from the bits and pieces we know, though we can certainly define a lot of adverse outcomes.

Edited August 22Aug 22 by CharonY
exchanged word which didn't make sense.

2 hours ago, CharonY said:

I think based on the molecular knowledge we have now, we can move away from the original rough hygiene hypothesis and dig a bit deeper into mechanisms.

A close schoolfriend graduated to become a junior doctor at St Georges, Tooting at the same time as the resident epidemiologist Professor David Strachan was popularising this idea, and I must admit that I was much influenced by her enthusiasm for his work.

However, in my current abode, there are health threats (typhoid, the haemorrhagics etc.) that are not seen too often in Tooting. You really can't play fast and loose with them.. In the long term, you won't win that one.

2 hours ago, CharonY said:

The bottom line is that the immune system is an incredibly complex system which many interactions without body and its inhabitants.

This intrigues me (even if I don't quite follow some of the wording) as the strategy I've settled into is a diet based on 'dodgy' veg from the local markets, that almost without exception is either pickling or fermenting in a Kilner jar by the following morning. Probably the most processed food I eat these days is my daily dose of sauerkraut, and I honestly haven't felt so well in years. If, as I think you're suggesting, this is due to selectively allowing certain organisms to chronically 'infect' me, then I see no reasonable grounds, based on personal experience, to dispute this newer interpretation. Though I still might take my annual dose of worming pills just to be on the safe side. Some of them are definitely a bit nasty.

2 hours ago, sethoflagos said:

A close schoolfriend graduated to become a junior doctor at St Georges, Tooting at the same time as the resident epidemiologist Professor David Strachan was popularising this idea, and I must admit that I was much influenced by her enthusiasm for his work.

However, in my current abode, there are health threats (typhoid, the haemorrhagics etc.) that are not seen too often in Tooting. You really can't play fast and loose with them.. In the long term, you won't win that one.

This intrigues me (even if I don't quite follow some of the wording) as the strategy I've settled into is a diet based on 'dodgy' veg from the local markets, that almost without exception is either pickling or fermenting in a Kilner jar by the following morning. Probably the most processed food I eat these days is my daily dose of sauerkraut, and I honestly haven't felt so well in years. If, as I think you're suggesting, this is due to selectively allowing certain organisms to chronically 'infect' me, then I see no reasonable grounds, based on personal experience, to dispute this newer interpretation. Though I still might take my annual dose of worming pills just to be on the safe side. Some of them are definitely a bit nasty.

It is a bit difficult to explain. The way I see it, there is really no clear optimum state of the immune system (at least as I understand it). Rather I now tend to think of it as a series of potential equilibria that are governed by an incredible number of factors, ranging from genetics, age, exposure to pathogens and other antigens through one's life history, diet and so on.

All these variables are acting on each other in a way that we do not really understand in detail. For example, diet has some impact on overall inflammation, though the devil is in the details. Fermented food has long been discussed as potentially anti-inflammatory with pro-biotic potential. At the same time, especially Sauerkraut has found to have high concentrations of biogenic amines, including histamines. However, it seems to be mostly a problem in folks who have histamine intolerance (and then the question is why the folks are intolerant).

So clearly, there are significant knowledge gaps and in many cases it is insufficient to merely monitor what is chemically or biologically present and link it to a particular outcome, especially on the individual level.

Edited August 22Aug 22 by CharonY
Edited to finish a thought.

I should add, fermented foodstuff frequently has plenty of (mostly) harmless bacteria. Antigens from them are likely also interact with our immune system and potentially mitigate responses. Fundamentally, I would prefer priming of the immune system with those, rather than with helminths. The latter are likely able to better suppress the immune system (due to reasons mentioned earlier).