In our lab we call it the lock and key hypothesis:

One size doesn't fit all: unraveling the diversity of factors and interactions that drive E. coli urovirulence https://pubmed.ncbi.nlm.nih.gov/28217693/

Bacterial virulence phenotypes of Escherichia coli and host susceptibility determine risk for urinary tract infections https://pubmed.ncbi.nlm.nih.gov/28330863/

It can be useful to look at infections from the perspective of microbes:

The acquired immune system: a vantage from beneath https://pubmed.ncbi.nlm.nih.gov/15539148/

TLDR: Microbes were here long before us and will be here after us. We are living in their world and the more we try to fight them head on, the more they will bother us. Best to adapt and co-opt.

Microbes love on every square inch of the world, or close enough to it compared to humans.

Humans live like shower fungus at the local gym, we live in the cracks and near the water sources, on the scale of earth we might as well be microscopic.

> on the scale of earth we might as well be microscopic.

The total biomass on earth is about 6x10^9 t whereas the total mass of the earth is about 6x10^21 t so all life on earth is microscopic on the scale of the earth. Also, your choice of words implies you’re mixing up quantity with quality. The fact that we’re microscopic on any scale doesn’t mean we’re as worthless as shower fungus. We churn up mountains to get a microscopic amount of gold by comparison because the gold is worth more than an average mountain.

That's a calming thought.

All biomass on Earth is a one with 12 zeroes less than the mass of the Earth.

Your brain is about 3 regular bottles of water worth of mass.

Whatever inside that brain of yours that is stressing you out... is so far from being consequential to the universe that it's probably not worth stressing about in the first place. Just relax and enjoy the ride through this crazy universe.

> Your brain is about 3 regular bottles of water worth of mass... is so far from being consequential to the universe

And yet how much is one thinking and perceiving brain worth compared to 26 sextillion unthinking stars and 100X as many dead planets? I would say it’s priceless by comparison. The rarest gem worthy of a lot of “stress” to cherish and preserve, although personally I’m quite sanguine!

yet, some brains can change the world. i don't think that's a very inspiring way of thinking about the kind of impact we can make.

This is excellent but also galaxy brain level. Not something that's ready for popular digestion, given the levels of basic science denial that have popped up post COVID, even among supposedly empirical communities like tech.

Eventually if this gains more predictive power then it can be merged with germ theory and explained better to the public.

I didn't read the whole thing just the abstract, but isn't this just the modern standard view?

Germs cause disease. Your immune system stops germs. To get a disease the germ must both get into you and either overwhelm or find a way past your immune system.

This hardly seems like something beyond public comprehension.

I also found it a bit too philosophical in the sense that we can already explain a lot of the variations in outcomes to infection.

For example, HLA/MHC is a family of genes tasked with the presentation of antigens (e.g. chunks of proteins) from pathogens and your own cells to the immune system. It is a very polymorphic region, i.e. full of genetic variants that lead to lots of differences in the peptides that are presented, to stop spread of infections at population level.

If you have one of the lucky/unlucky alleles, you will have high chances of protection/susceptibility. Some alleles, like HLA-B57, protect against HIV but it's a tradeoff. Carriers are much more susceptible of autoimmunity [1].

From an environmental point of view, if you have dysbiosis, e.g. if your gut microbiome ecology is altered, T cell receptor distributions will be altered and you are more likely to have a bad response to certain infections.

[1] Effects of thymic selection of the T-cell repertoire on HLA class I-associated control of HIV infection. https://www.nature.com/articles/nature08997

The article doesn't contest that view but instead considers how germs are an orthogonal dimension and that we are starting to understand better that the host and all of its cells, not just some ill defined subset called immune cells, are responsible for host health and that when functioning properly can coexist with germs without letting them cause disease.

I wonder whether this perspective aligns well with research into bat viral reservoirs as they exemplify this model.

Isn’t this like saying that sunburns are not caused by the sun but by an inborn lack of melanin production in fair skinned people?

Is our vulnerability to bullets a deficiency in the host? If we had tougher thicker skin we might be able to withstand at least lower caliber shots.

Seems like just a weird way of looking at causality.

Yes to all!

Although I think your final point is the most profound.

Dubos' "second thoughts" may have been lacking in practical application or perhaps even totally pointless, but:

    Is our vulnerability to bullets a deficiency in 
    the host? If we had tougher thicker skin we might 
    be able to withstand at least lower caliber shots.

For the bullet analogy to be apt, we'd have to have a reality where nearly all people have bullet-resistant skin and only a small minority of the population could be injured by bullets. Then, yeah, it would be worth looking at why those people had malfunctioning skin.

The reality is that the vast majority of germs do not cause disease. Most people with latent TB do not develop TB; most people with latent herpes zoster do not develop shingles, etc.

Honey badgers are bullet resistant.

Everybody already knows that stress can trigger a herpes outbreak; it's common knowledge that holistic health and environmental circumstances play a major role in whether or not an infection manifests as disease. Who ever said otherwise?

Maybe I'm missing something, but it seems like this guy is burning a strawman to seem profound.

Agreed; the germ theory of disease simply says infectious disease X doesn't occur but for some kind of microbe. That is, the x-factor isn't bad air, evil spirits, or offending the gods.

It's obviously not true that if you get infected by microbe m you will get the disease X. Such claims may be overstated to motivate people to get vaccinated or to practice good hygiene or animal handling.

What the author seems to be arguing is that medicine has over-emphasized microbes, and under-emphasized the role of immune system deficits, particularly for diseases where latent infections are common.

    it's common knowledge that holistic health and 
    environmental circumstances play a major role in 
    whether or not an infection manifests as disease

I'm understanding the linked article thusly: Dubos wasn't disputing the facts of germ theory, as his provocative choice of titles may have suggested. He was wondering if we should pursue a host-centric approach rather than a germ-centric approach to medicine.

It is perhaps roughly comparable to (for example) you and I both agreeing that UX and backend engineering are important, but disagreeing which of them should be the primary lens through which we tackle the software development process.

In the end though, yeah, "germ theory vs. host theory" is probably kind of a moot point in 2023. Early application germ theory was basically, "how do we kill germs?" whereas I think that the last XX years of medicine have been more about the holistic interaction of germ and host.

I do not work in the medical field so I would obviously welcome more knowledgeable feedback.

> Everybody already knows that stress can trigger a herpes outbreak

Also stomach ulcers, psoriasis and so on.

Every knows this now. This was an extremely hard fought against piece of medical knowledge though, from my understanding. Up through the 80s and 90s it was a radical view.

Now, fortunately, it's got a fancy name (psychoneuroimmunology) and is treated as an important field of study, as it deserves.

Interesting thoughts but I don’t see any as ground breaking. The author correctly points out that there are clear genetic conditions that predispose someone to a disease or protect from one.

Germ theory correctly describes infection as a root cause of illness. It is true that most people who are infected do not show develop disease symptoms and this does mean other factors are at play. Stress, environment, age, and genetics all play a role in whether a person develops a disease or just maintains a latent infection with no symptoms.

This article adds a genetic component to a previously published host theory printed in 1955. In todays world I think the idea of germ theory and host conditions including genetics is well understood by most in the medical community.

Host theory has been applied since Africans tolerant to typhoid/malaria/yellow fever were brought to the New World...

Another way to say it is that just as in eukaryotes, just because a gene is found in the genome of a microbe does not mean that associated protein will be expressed.

The genes could be under tight regulation (e.g. epigenetic) and only get accessed in specific instances/people.

Let's not forget, it's not in their best interest for microbes to kill you quickly, it's better to replicate and spread. You can do that as a pathogen, or you can do that as a friendly member of the microbiota.

There are also mechanisms which "tame" the microbiota, such as the continuous secretion of mucus which is extremely diverse in its arrangement of sugars which continuously feeds the microbes but doesn't let any one metabolic strategy take over.