One of the geneticists who worked on identifying this is also on HN and tried to explain this [2] but HNers think they are smarter than actual leaders in the fields of genomics.
[0] - https://www.mpg.de/10973923/why-do-scientists-investigate-mi...
[1] - https://www.mpg.de/8949327/structural-variants-crispr-cas
Or in other words the meat of the critique is not aimed at genomics, but rather in science marketing.
The reality is every theraputic has some kind of negative side effect, which may reduce the incentive for it to be productionized becuase the whole point about medicine is harm reduction.
Passing the hurdle of being viable in mice is a major hurdle because in most cases, experiments fail. And if it's efficacy is proven in mice, it shows viability in a specific approach and justifies investing the hundreds of millions of dollars in trying to bring something to Phase 3.
Right and if that is such a good thing why are those macrophages not always on alert. I smell longterm cancer or similar.
Or simply autoimmune reactions which can be devastating.
The classic example is asbestos related mesothelioma. "Frustrated phagocytosis" is the name for the way macrophages become locked in a never ending spiral of eat, die poison loops around the asbestos.
Do we really want macrophages to go into high gear? Will we make sure no one who has it has been exposed every to any asbestos?
What about other triggers of frustrated phagocytosis? People who commute by subway (tiny metal particles).
The point isn't to say that this is a bad idea necessarily but that I'm not sure this sounds so much safer than regular vaccination.
The target does matter, that is the basis for the whole technology, and the thing most predictive of efficacy. That's why the flu shots often don't work and the shots for smallpox and measles do, the flu is a more rapidly mutating target.
Going crazy with the adjuvants was popular during the pandemic when it became clear that the virus had mutated (the target protein), but no one wanted to do R&D for a new target. Counting white blood cells became a proxy for efficacy, and you can manipulate that stat with adjuvants.
https://www.science.org/content/blog-post/mrna-vaccines-and-...
But critically this isn't as important as people think. The primary goal of the flu vaccination is of course to temper spread of the main viruses that season. But it's also to build people's immune library of exposure to flu viruses.
Recall that the 1918 "Spanish" flu was so terrible not because it was intrinsically a worse virus but that it was one which many younger generations had not been previously exposed.
COVID has meant that many younger generations again has a much smaller library of past exposure.
[0] https://www.cidrap.umn.edu/influenza-vaccines/estimated-effe...
>There may also be consequences to dialling up the immune system beyond its normal state – raising questions of immune disorders.
> Jonathan Ball, professor of molecular virology at the Liverpool School of Tropical Medicine, said the work was undeniably "exciting" but cautioned "we have to ensure that keeping the body on 'high alert' doesn't lead to friendly fire, where a hyper-ready immune system accidentally triggers unwelcome side effects".
> The research team in the US does not think the immune system should be permanently dialled up and think such a vaccine should be used to compliment rather than replace current vaccines.
That way, your immune system wouldn't be on continuous high alert, but you could give it an "Oy, wake up. Incoming pathogens." blast.
What has no relation at all to what possible side effects this could have.
The body is like legacy spaghetti code written by hundreds of teams of outsourced engineers. It mostly works. Just never remove any commented out lines or it may break.
There's also no reason we shouldn't be immune to funnel web poison: cats make an enzyme which deactivates it, whereas primates don't.
Naming departs from technical accuracy when adopted by the masses, as they retrofit their common understanding. Wouldn't be too surprised if "vaccine" ends up covering other strong defense-boosters.
https://knowingfabric.com/mushroom-leather-mycelium-sustaina...
is pretty neat
In aviation, autopilot features were until recently (and still for GA pilots) essentially just cruise control: maintain this speed and heading, maintain this climb rate and heading, maintain this bank angle, etc.
"toll like receptors"
https://pmc.ncbi.nlm.nih.gov/articles/PMC7173040/
https://www.sciencedirect.com/science/article/pii/S135964462...
https://link.springer.com/article/10.1186/s40364-022-00436-7
there's probably a reason evolution didnt put the immune system on permanent "amber alert" as they call it in the article
Amber alert means something different than the author thinks ...
https://en.wikipedia.org/wiki/Red_Alert
This is just an idiom for denoting a high alert state.
So a macrophage on "red alert" would be reacting to an active infection or disease.
It would just be temporary, but there is likely trade offs.
Until we find out why nature made it so some of us kill ourselves maybe we shouldn't fuck with it? Remember Chesterton's Fence.
Now, you could have restated this in a better way IMHO. I'd put it like this: are there any evolutionary advantages to having worse-than-average near or far vision? For example, we can imagine that people who had extremely good long range vision would be more successful in hunting, and perhaps- this is where I'm speculating heavily- having poor long vision is compensated by having better detail vision for fine tool work. However, what I've learned after many years is that attempting to perceive the true nature of the evolutionary fitness function is challenging.
As for your bit about suicide: please be a lot more thoughtful in speculating about suicide.
"Sorry son, you can't get these glasses. It's for the betterment of humanity."
Remember that cephalopod brains are donut shaped and their digestive tracts go right through the middle and if they eat something too big they'll have an anyeurism. Pandas and koalas evolved special diets that serve no evolutionary purpose and both would be extinct if humans didn't find them cute. Sloths have to climb down from trees to take a shit. Female hyenas give birth through a pseudopenis that often ruptures and kils them. Horses can't vomit and if they swallow something toxic, their stomach ruptures. Also their hooves and ankles are extremely weak and not well designed to support their weight. Numerous species like the fiddler crab and peacock have evolved sexual displays that are actively harmful to their survival.
And as for humans, our spines are not well adapted for walking upright, our retinas are wired backwards, and we still have a useless appendix and wisdom teeth. The recurrent laryngeal nerve has an unnecessarily long and complex route branching off the vagus and travelling around the aorta before running back up to the larynx.
Evolution is not smart. Evolution isn't even stupid. It isn't trying to keep you alive and it isn't even capable of caring if you die. Yes we should absolutely fuck with it, because we don't want to live in a world where we still die of sepsis and parasites and plagues because "we don't want to mess with evolution."
Sometimes things get trapped in a local minima. Particularly when a seemingly inconsequential detail at a much much earlier stage becomes a dependency of lots of downstream stuff, but then it turns out that this just so happens to conflict with a better option in the here and now.
More commonly, the "perfect" solution is extremely brittle while the (supposedly) "good enough" solution is incredibly robust to all sorts of environmentally inflicted bullshit. In other words, most of the time evolution is practical while the humans criticizing the outcome are ignorant idealists.
That's it: and it's separate from good enough because that can include things like "happened to live on the part of the island which didn't get obliterated by a volcanic eruption at the only point in history that volcano ever erupted".
Koalas biggest problem is us? Like they seem perfectly adapted to their niche. Eat lots of leaves that nobody else is adapted to use as food, and once a year, run very fast to outpace the bushfire that your principle food source needs to reproduce.
This was believed in the 20th century, but we now believe the appendix is actually useful, and is basically a fail-safe in case the intestinal flora are wiped out; some will survive in the appendix and repopulate the intestine.
I personally look forward to every innovation that potentially improves our baseline.
You can just stop taking antibiotics and vaccines.
Those are way more interesting odds.
You wouldn't want to get vaccinated for smallpox in the middle of a plague epidemic, because that would waste your immune system's resources on an extinct-in-the-wild disease, when it really needs to be gearing up to stop the plague killing you.
You do not somehow go into deficit by getting a vaccine.
They speculated that immune systems evolved to avoid being continuously on alert. And that's exactly right- our immune systems have an extremely complicated system for detecting foreign invaders that is tightly regulated. And a failure to regulate that is often associated with autoimmune disorders, which remain very poorly understood.
I've studied biology from the perspective of engineering better drugs for decades now and I can say with confidence that I simply don't understand how the immune system works, and I don't think anybody else really does either (compared to, say, the heart, or many biological systems like protein production). We have identified many players, and observed a great deal of actions, and have speculative models for many of the underlying processes, but we don't really have an "understanding" of the immune system. I skimmed this paper and frankly, it has a very long way to go before people are convinced to try this in human clinical trials.
I look forward to innovations, but to a first order approximation: evolution found model parameters that exceed the best human science and engineering.
The treatment also supposedly activates macrophages in the lungs (and thus not elsewhere). Only some small particles and vapor droplets from foods go into the lungs.
The world: Announces cures for half a dozen cancers, and the common cold