Mosquito saliva alone has profound effects on the human immune system (2018)
journals.plos.org
journals.plos.org
https://www.caryinstitute.org/news-insights/media-coverage/h...
Utterly fascinating. Our bodies are so much more complex than I could have imagined.
https://en.m.wikipedia.org/wiki/Octopus under pluralisation
Interestingly:
> Historically, the first plural to commonly appear in English language sources, in the early 19th century, is the latinate form "octopi"
That’s quite late and interesting the “wrong” one was first.
It’s only platypuses if you see more than one at a time, and that’s pretty much never gonna happen ;)
I have never seen nor heard anyone write or say “platypi” before now. Some web sleuthing suggests that platypuses is somewhere between 20 and 100 times more common in English.
Platypuses don’t live in North America. Most of the older sources that Google n-gram is pulling from for the above chart are British or Australian.
A substantial proportion of the recent uses of platypi are grammar guides telling people that it should always be spelled platypuses.
with vanilla ice cream
By the way, how do you pronounce octopi? Is it "octo-pee" or "octo-pie"?
(Or you know, we could do both.)
Life, uh, finds a way.
So I wouldn’t advocate for that approach.
From age 30 onwards, I suffer them as much as the next guy, not sure what could have changed since.
If you drank the same amount of 0% ABV water in that time, you’d probably die of water intoxication, so I’m not sure any adverse effects of the alcohol would be noticeable.
Point is it could be a lot of alcohol for the mosquito.
No, the alcohol wouldn't. Unless you distilled all that beer and ingested the alcohol alone. The massive liquid intake would kill you though.
The liver doesn't store alcohol, so how many grams you ingest in total doesn't matter, only in what concentration. Keep in mind that alcohol is perfectly soluble in water too.
(~10 pints of blood in the donor, 1/10 of a lot of alcohol...)
On the other hand, we've probably made more progress in that understanding during the past 100 years than in all of the time before that. So, if our rate of knowledge acquisition is increasing, maybe that upward hill isn't quite so steep.
For example while dogs have a much shorter lifespan than humans they seem to face all the same age-related declines humans face. This holds for animals close to or exceeding our mass as well. If different parts of the body wore out simply due to e.g. mechanical stress, you would expect e.g. dog joints to be perfectly healthy after 15 years since they are biologically very similar to human joints, when in fact dogs tend to still have arthritic and otherwise fragile joints at 15 (or earlier).
Everything declining together, just on different timetables in different animals, seems to suggest that aging is controlled by either a single mechanism or some interwoven set of mechanisms that cause everything to fail at the same time, rather than individual parts failing because "they wear out." If you could target that mechanism(s) then maybe you can make humans live as long as e.g. tortoises. But of course we haven't confirmed that such things exist, but the above is at least some motivation for why they might exist.
Without a coherent theory of senescence this is all conjecture, but there's compelling evidence that there's some set of hidden variables we aren't seeing that is "pulling the strings" when it comes to aging.
Let's just think logically about it for a bit. Your cells come with all kinds of repair machinery and redundant DNA encoding. All cells do. But there are single-celled creatures that don't age and reproduce by cell division, and they haven't lost their function despite billions of years and millions of generations. Same for humans and whoever else reproduces sexually — there's A LOT that needs to go just right for a new human to be born, including making billions of copies of parents' DNA, yet it does work just fine most of the time. This tells us that the DNA copying process must be very robust, and that with age, it's these mechanisms that keep everything in check that deliberately get weaker or stop working altogether.
Recent research proves it.
For example, there's evidence that organisms propagate their age throughout all tissues using some kind of signaling in the bloodstream: https://www.nature.com/articles/ncomms13363
Even more bizarre, the aging clock, as determined by DNA methylation, gets reset to zero at the beginning of embryonal development: https://hplus.club/blog/how-and-when-mother-nature-resets-th...
There are definitely a number of processes involved in aging that are pre-programmed as you suggest, namely the hormonal clocks involved in puberty and maturation, and then later senescence.
It's not particularly useful to compare humans/mammals to single-celled organisms, which operate under way fewer constraints. They don't have to deal with cancer, as just one very basic example. They also don't have to figure out how to clear old junk from their tissues and individual cells. They just start over with a clean slate every time.
Signals in the bloodstream - various hormones and immune cells - are obviously involved in aging. But there are many of them, and we are just starting to understand their different interactions. There is no doubt that aging research is going to yield ways to suppress or promote the action of certain hormones, replenish/reactivate certain stem cell populations, etc. but better understanding of intercellular regulatory networks is needed for that.
To call DNA methylation the determinant of an "aging clock" is also too narrow or simplistic. DNA methylation is the mechanism of cell differentiation, but it's "metadata" that has to be copied over between cells when they divide, just like the DNA itself. Early in embryogenesis, the DNA methylation pattern is reset and overwritten using the regulatory cascade of master control genes (homeobox, etc.) - so it is expected that the methylation pattern will have lower fidelity with each division cycle before or after that point.
This is the golden age of biology - we have just gotten a hold of the tools that will let us solve these problems - but it's messy and complicated. Investing in your understanding of these processes can have a huge payoff - I recommend reading some of the Nature Reviews articles like https://www.nature.com/nrg/ - I've always found them to be incredibly helpful in summarizing the state of the art.
While that makes it really unlikely that aging can be reversed, it certainly isn’t logically impossible. All you need to do is expell the chaos, and get one good quality regeneration (possibly taking about 7 years) and then you’d be right back to 18 years old again. That might make it worthwhile enough to be willing to have your body burned by a billion laser shots and float in a vat of liquid for 7 years. We might get to find out in our lifetimes? who knows.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712935/
Also consider that long life may not produce the advancements you might hope for. There's a saying: "Science progresses one funeral at a time." It's a reference to the fact that individuals typically hold fast to their ideas-- scientists included. Certainly we may react to & integrate new knowledge, but at some fundamental level we are hindered by the cognitive foundations of knowledge laid down when we're younger that are not automatically escaped on new information. That's not even accounting for pride & ego causing people to cling even more fiercely to their own ideas.
You might think that on ongoing infusion of new talent would prevent this, but massively extended age would also entrench the older generations firmly into the power structures of the scientific community, creating at least a partial gerontocracy. Heck we have a bit of that now: Plenty of PhD candidates get stuck "playing the game" and not bucking the status quo too much, only guided down paths their advisors find acceptable. If you have something that significantly contradicts the current consensus, then without a very good & open minded advisor willing to go to bat for you, you might as well shelve it, do something mundane & acceptable for your dissertation, and dust off that other idea when you're done. This situation would not improve with the further ossification of power structures.
If we got there though-- massively extended lifespans, the gerontocracy aspect of things in society in general would be also be a difficult sociological issue. With a 300 year lifespan, by the time you got to 200 you would probably consider anyone under the age of 50 as little more than children. The issue of wealth inequality would be incredible as generational wealth accumulated by anyone remotely careful with their finances would, by late-middle age, dwarf the resources of anyone starting out.
There could be some interesting & positive aspects to all of that though too. Imagine have half a century to explore intellectually or otherwise before you were expect to settle into a path in life. And if we found societal of medical methods to help people break out of psychological & intellectual inertia then a person might expect to have multiple very different careers in their lifetime.
Anyway, all of that would be a very long ways off. At my age I might still hope that leaps in medical advances could give me an extra 10 years of productive healthy life, but probably not much more. And I've also gone a long ways off the original topic, so I'll end it here.
You might be able to restore the body's ability to regenerate itself. But that's a terrible idea. I shudder at the idea of living to 120, never mind 200. Imagine being born in 1821 and having to live today. Imagine how confusing that would be.
Next time someone asks me to do the dishes, I will tell them the same. Hopefully they also forgot about the sun providing energy into the system.
Don't cheat! Don't use the caloric needs of a fully grown adult. Their bodies stoically accept a lot of the damage done by entropy. You have expend additional energy to reverse it.
Don't cheat, remember to account for a population growth rate == the current birth rate.
If you don't like having to account for the growth rate, please give a moral explanation for why some select few get to live forever and others croak.
How much power do you need? How are you supplying this power? It's cute to say "Sun". But solar panels (let's assume 100% efficient) require surface area that would otherwise be used by plant and animals for their existence.
So live forever by
1. Radically transforming the Earth into a massive ball of polycrystalline silicon 2. Giving eternity to only a (very) select few.
We are not closed Systems
The live forever types are just assuming that energy will be plentiful enough to sustain hundreds of billions of people indefinitely [1] and heat easy to dissipate
[1] The population of the earth is stable at 7 billion only because people have this nasty habit of dying. If we stopped doing that, the population would grow exponentially at the birth rate of 1.7%. Or a doubling every 42 years. In 160 years (not that far off from the current record of longevity) the world's population would hit 100 billion people.
Of course the "live forever" types never mention that eternity is a promise for the privileged, and not for the masses.
As long as changes happen gradually, I don't see the problem. If they don't, people of almost all ages will be confused.
So you're in-between the age of 40 to 60? Let's say you're 60, born in 1961:
- Your local pop radio station often plays a rock song from your adolescence. The Queen of Pop whose posters adorned your room and so scandalized your grand-parents still sings at the Super Bowl.
- The Star Wars movie you geeked out as a teen/young adult has become a billion dollar franchise your grandkids drag you to
- The ATM you learned to use thirty years ago are still around basically unchanged.
- the quarter the tooth fairy left you as a kid that you found in the tin can of boyhood treasures is still accepted as currency
Compare that to a 60 year old person born in 1820.
They have yet to have seen a train: most people in the world at the time lived their whole lives in their villages far from any railroad. China's first railroad was built in 1875, and quickly dismantled. (China, alone, in the 19th century had between 30 to 38% of the world population)
Most likely this person lives in feudally arranged society. The emancipation of the serfs in Russia was in the mid 1800s, and that was the last of the European countries to remove feudalism.
In the anglo saxon world, women were effective properties of their spouses.
The superiority/inferiority of races was obvious to the learned classes.
Slavery was practiced throughout the world except Europe and then the US.
Homosexuality was punishable by execution most everwhere in the world
Sexual roles were well defined and strictly obeyed according to local customs (i.e. they weren't universal norms, but norms existed universally).
The only way to fly was in a hot air baloon. The only people who ever witnessed this lived in Paris or in London
Steel existed but was extremely expensive and not used for construction. Wrought iron was used instead, and it was a brittle mess that resulted in catastrophes. As a result the buildings in urban areas were typically no more than 6 stories high. Religious buildings were much taller, but projects that took centuries to build.
Communicating with someone across the Atlantic took weeks.
Now, let's say our hypothetical person living in 1880 and born in 1820 lived another 60 years.
The airplane is invented and used to devastating effect in multiple wars
The automobile is invented, and by 1940 mass produced.
Throughout the world, therefore, buses provide transport to remote area that aren't serviceable by rail
Skyscrapers pop up.
A world war has impacted most people in the world. A new one has just started.
A communist society exists and has mechanized death killing millions.
Telecommunication, first by wired-telegraph, then by wireless telegraph, and finally by radio exists and enables instant communication across the globe. The most remote villages can receive the BBC world service, often in their native language.
Our gentleman most likely wouldn't be aware of this development but classical physics has been shattered, the concept of time turned upside down. The atomic era has also begun, but most people will be blissfully unaware for another 5 years.
Penicillin is about to revolutionize life expectancy.
I think this person born in 1820 would be very uncomfortable if living today.
Unless you're religious. Then it's not death you should fear, but the judgement.
To keep with the programming analogy, ya, you can see the SUM statement and that is necessary to understand, but what is it for? What is it's role in the larger program? Where do it's inputs come from? Where do they go? What effect does changing it have in other places?
I do agree our knowledge of genetics etc. will be much expanded soon. But we'll probably also make some nasty errors.
Yes, the interactions are the interesting bit. Perhaps we can figure out the biological pathways at the cellular level by taking a systematic approach of turning genes on/off and turning their expression on/off, then looking at the expression of other genes. This is exactly what could be done by robots.
This is simply not a problem we’re going to computer our way through, at least until we have large scale quantum computers and way better data than we have today.
To my knowledge, while we can develop a statistical assessment of a vaccine's safety, we can never know how the vaccine will affect a specific person that takes it. My argument here is that the human body is so fantastically complex that no two cases are ever the same, and so the only way to know how a vaccine will affect a person is to run the experiment, by having them take it.
I think this is one attribute of what are called "Wicked Problems": The only way to know if a change is going to be an improvement or not is to make the change and see how the system state evolves forward in time.
Is this roughly correct?
Would you say that hopping on a plane is an experiment in testing if it will crash? When you know it very likely will not?
For example there is a reason we test drugs on mice, because they are pretty similar to us (mammals), of course there are also differences.
I like Kevin Kelly’s technium concept. We are merely an extension of evolution and our purpose is to continue it, which we do willingly and unwillingly.
The reason for this is that living things are evolved, rather than designed.
We have seen that even in very simple hardware, when using a genetically evolved design, we end up having circuits that functions as per the requirement [1]. But it ended up being very hard to figure out how the thing actually worked, and when components were removed that seemingly did not have any purpose, the thing stopped working.
And this, in my opinion, points to a very important aspect of evolved systems. We can only have a statistical assessment as you say. But no way to say for sure that, "This and this alone will be the only effect of an intervention".
But we can have some idea, depending on the type of intervention. For example, we can say that something that was part of the evolution, will not interfere with its working, simply because evolution has taken it into account during the process. And here comes the concept of something being "natural" to the organism. So we can say that stuff that is taken orally, is much safer than injected stuff. All through our evolution, we have been taking stuff orally. So a Vaccine is much more like throwing a spanner into our workings, than taking something taken orally. Similarly stuff that were part of our natural environment, during evolution can be considered as safer, as opposed to stuff that were not.
I think this is why mocking the concept of "natural", by saying, "Everything is natural, because it is found in nature", is embarrassingly missing the point..
[1] https://www.damninteresting.com/on-the-origin-of-circuits/
One side (the mainstream) claims vaccines are effective and safe. The other side, claims that no, we do not in fact know that the vaccine is safe and therefore you should not get it and take your chances with the disease.
The problem is that we don't in fact know that the vaccines are truly safe for everyone, because mRNA technology (while incredible) is new, but from my personal interactions I've observed that most intelligent people see that getting the vaccine increases your expected quality of life given you've never had COVID before. However, those who don't believe this will take any claim made by the mainstream (vaccines are safe) as evidence that they are hiding something, further deepening their suspicions.
This is a feedback loop; the more people that refuse the vaccine, the more the mainstream will push for more vaccinations, causing more people to refuse the vaccine. All because the nuance of "we don't know that this is as safe as taking a walk in the sun, but we have solid evidence that it improves your E[QOL]" isn't easy to communicate.
Hesitancy around covid vaccines isn't the antivax of the previous generation, and responding as if it was won't help anything. Actually having an honest conversation with the public that you're more likely better off with a vaccine is not an easy concept to communicate (as you correctly point out), but it would be a good first step in trying to rebuild that lost trust.
Cuomo was held up as a great example when it looked like he had done a good job, but then when screwups were revealed opinions rightfully began to change.
By all means let's point out the ridiculous partisan aspects of this debacle, or out & out screwups like initial mask guidance. But also recognize that in plenty of cases a change of stance is not partisan or contradictory, it's the rational response to new information.
The challenge is that guidance not regularly delivered with any caveats or margins of error. I think this is a mechanism to try to drive compliance up through a posture of confidence, but when the guidance ultimately flip-flops it just looks like either people are lying or they don't know what they are talking about.
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https://unchartedterritories.tomaspueyo.com/p/delta-variant-... discusses "The Hammer and the Dance", an article published in March 2020, that correctly flagged the risk of mutations.
https://twitter.com/WSJ/status/1368229958158610435 https://www.wsj.com/articles/covid-19-variant-in-brazil-over...
WSJ, writing in March 2021: "countries such as Brazil risk becoming a breeding ground for potent versions of the virus that could render current Covid-19 vaccines less effective, public-health specialists warned." Biden's "wear a mask until you do" was in May - very irresponsible.
It would go a long way in these discussion if you make it clear which vaccine you are talking about.
At some point you have to decide to balance the risk in some way and make a choice. Or live your life in a perpetual state of epistemic uncertainty & indecision. In most cases people are fine doing this: very few people refuse to drive over the unlikely possibility of a fatal car accident, or live in a basement on the remote possibility that a tree or meteor will fall on their home.
Unfortunately in this case, politics entered the equation. People cling to epistemic uncertainty to justify consistency with their political allegiance rather than make a decision on the basis of balanced risk, because they they have chosen a balance point that would make them an agoraphobic recluse if applied consistently across their life.
I withhold that judgement for those who are reluctant due to the "emergency" approval (in the US) but plan to get vaccinated when fully approved (which Pfizer now has received). I might disagree, but I think a rational person could still balance their risk on that "emergency approval" point. So long as they also are consistent in their application of risk balancing to recognize that strong precautions to avoid infection were required in the meantime.
That is because there is no media that is fear mongering on these things by reporting 24x7 on every car accident in gruesome details, and run reports on how driving in a car is very dangerous, when there is a chance that one of the thounsand other drivers that you come across on the road might be a crazed, drunk, distracted person that could hit you, support it with "statistics", and just because you survived the last trip, does not mean that you ll survive the next.
They will also run stories about these "anti-walk" persons who took a car or bike, but died in a horrible crashes.
The point is, everything is a line between risk and benefits, and when the risk and benefits are a matter of perception, media has great potential to come in and set where that line is..
But it didn't happen even after so many years, so we know that drinking water did not make us less capable.
I genuinely had to google reviews about it, and then still check if 50C temperature is safe for skin contact.
Torture comes quite close to it, still I hate mosquitoes even more.
Even now I only use the 3 second setting and sometimes I can't stand it.
Most people think that Amazon sells all the products on their site - because Amazon designs their site to look like it. Even young people who are technically literate are fooled. This results in a lot of harm..
https://arstechnica.com/tech-policy/2021/08/amazons-plan-to-...
In actuality, eBay is more of a trustworthy marketplace than Amazon...
In the interest of making more art available to more people, independent of spending-money, I’d rather us collectively invest more in public libraries. To what degree do public libraries fund authors?
Which sucks, because I otherwise have eliminated Amazon in my life.
Listings are often even hijacked!
https://news.ycombinator.com/item?id=27684807
(And Amazon couldn't care less!)
Then you factor in the astroturfing by contracted subsidiaries through shilled comments and votes/likes/dislikes all over the broader internet.
My advice is to get used to the downvotes. When there are few comments but many downvotes, it's pretty indicative of a poor attempt to suppress valid information. They have no counter arguments, just a supression button. Consider your task accomplished. ;-)
Usually in the woods I don't have a hair dryer with me. So you are using it if you get bitten in the backyard or if you get back home from the hike?
Usually I also notice bites the next day when they start itching or when I get evening shower unless I really slap that mosquito in the act.
Did you actually read my message?
Edit: posted this comment before reading other comments so didnt realize others have also suggested the same.
For what it's worth my hair is so short I never owned a hair drier until I heard about this trick. So I bought a cheap one and it's only used in summer.
I think the hot spoon that others have mentioned is also worth a try as the circumference of the bite and spoon could keep non bite areas from burning.
WaPo link: https://www.washingtonpost.com/dc-md-va/2021/07/30/oak-mites...
Archive.is link (no paywall): https://archive.is/AEi6a
A mosquito has never left a mark or made me itch in my life. Poison ivy on the other hand…I could look at it and get a rash but not the go to the doctor rash.
But I have noticed often enough to note the difference. For me, the smaller, more stealthy mosquitos give me the small, temporary bump, but the larger more noticeable ones like the tiger mosquito or what we call zebra mosquitos (I think they are actually western encephalitis mosquitos (!)) have a more dramatic reaction.
What are the profound effects?
What are Th1 and Th2 responses?
What are cytokines?
What are immune cell compositions?
Overall is this a good effect or a bad effect?
"Mosquito saliva proteins have numerous effects on the immune system, and we describe here the use of mice with a humanized immune system to study the effects of mosquito bites on human cells. Our results show that the number of immune cell types affected is much larger than previously described, and some immune responses to mosquito bites can be detected up until 7 days post-bite. The biological significance of these changes remains to be determined, but it might explain how some pathogens, such as viruses, can spread through the body in these cells, replicate to higher extents, and even remain in some tissues for far longer than detected in blood."
They're using stem cells to provide mice with "humanized" immune systems. The mosquito saliva is interacting with more types of immune cells than previously thought and remain active for longer than thought. The effects of these interactions is still unknown, but may be part of how bacteria, viruses, etc. carried by mosquitoes infect humans.
T Cells start as B Cells and then graduate from Thymus school after rigorous coursework (mainly don’t target and attack self). Most T helper cells stay as Th0 or undifferentiated. Th1 are specialized for inter cellular pathogens (bacteria and virus), Th2 broadly speaking are specialized for intra cellular pathogens (helminths and parasites).
Pathogens that have been around for a while like bacteria, virus, helminths, and parasites have evolved to push back against immune systems to varying degrees.
Source “The Body” by Bill Bryson
"If there's one thing the history of evolution has taught us, it's that life will not be contained... life will find a way". On the other hand, human progress moves way faster than evolution [eat that Darwin!]. That's amazing, but at the same time absolutely horrifying.
I always knew that the redness, itching, and swelling was an autoimmune response to the introduction of certain proteins present in mosquito saliva, so I'm wondering if it's possible to override that response by introducing enough saliva (with myself as a prime example), and what the wider implications of that are.
Sometimes I'll get a minor bump if in another country, must be a response to different proteins in the foreign mozzie saliva.
We already know that billions of humans have genetic mutations that specifically are there to protect us from mosquitos. So I'm not surprised that mosquitos have specific adaptations made for us either.
†I actually think we are symbionts. But people commonly just don't understand enough about how everything works to clearly see the benefits we get yet.
Do you have a source for that?
It would be impossible to collect the data but I would LOVE to see how longevity and mental faculty correlate with attractiveness to mosquitoes.
I get the arguments for both sides. I’d like less people to die from mosquitoes as well. I’d also like bats, fish, amphibians, birds, reptiles, etc to have an abundant source of food.
Some people's attitude is that these people (poor, far away, 'wrong' skin colour, etc.) might as well die for our beloved Nature.
We know enough to do just that - surgical removal is exactly what the gene drive solutions do. Even if we didn't, mosquitos are minor compared to the species being killed merely for profit.
>Imagine if some alien race was like: "we need to kill all humans", and then proceed and eradicate all the apes and monkeys as well?
I'd be a bit more concerned about the human part. I don't think I'll be available to care about the apes and monkeys. (Besides, the aliens are just being thorough and rational, and decided to make sure that we don't get evolved again. +1 for the alien team).
We still don't know the long-term implications of CRISPR applications on the entire species. However, it's already underway. Scientists are doing it and studying them in a lab setting. There's hope.
Not sure whether it's a good thing or not but now I am extremely cautious not to get any bites. This summer for example I avoided the backyard almost completely for this reason, with some exceptions when I covered myself in mosquito repellant spray. The mosquito candles I tried last time weren't very efficient in my case.
This makes me assume there’s some pheromone that could be extracted from a younger me, used to lure mosquitos to their death.
https://pubmed.ncbi.nlm.nih.gov/15311477/
I'm O negative and have always seemed to get the worst of it when out when friends.
I recently took up cigar smoking (yes i know) and anecdotally have found that I don't get bit as often if I've been smoking recently...to the point of watching someone six feet from me get destroyed while they avoid me completely. My father-in-law has been smoking for 50+ years and they ignore him.
Naturally, as soon as it came in the mail, I have yet to get a mosquito bite since.
I wonder if this could be a treatment for cytokine storms caused by things such as the spanish flu.
"humanized mice footpads" are a thing.
Many protocols use foot injury to look for heat shock response, immune recruitment, inflammation, etc.
There are monoclonal lines for gene knockouts, human chimeras, etc. to aid in certain types of study.
I wonder if it was mosquitos that have evolved to make disease they are carrying more infectious or it's the pathogen that evolved to take advantage of the mosquito's biology to make the host more likely to become infected. Regardless this is fascinating.
Two mosquitoes caught a soldier and one asked the other: should we eat him here or bring back home? To which the other mosquito answer: No, lets eat him here lest we want one of the big mosquitoes come and take him.
Source: close friend who served next to the Russian border.
I was south in Troms and down there they were so small we could easily kill them with a shovel or something ;-)