So I'm reading this book "In the Wake of the Plague" and the author reports that Black Death or the bubonic plague is very similar on a genetic level to HIV/AIDS. So close in fact that today's descendents of Black Death survivors of the 14th Century are immune to AIDS. Of course this works out to only about 15% of Caucasians. I wonder if this is true?
Another interesting similarity is the way both pandemics jumped from animals to humans. Black Death was a rat disease and passed to humans through fleas. AIDS was a primate disease that jumped to humans when someone ate a monkey somewhere between 1930-1950. Although Dave says humans caught it when a guy had sex with a monkey...not exactly sure who is right here!
It's kind of an interesting book, it charts the Black Death through medieval history and how it affected the reign of Kings and vice versa. FYI, did you know King Edward II was a homosexual who was killed by an agent on behalf of his former wife, Isabella of France, and the Catholic Church who didn't like that he had a French boytoy (and I guess also because he was a terrible King). He was killed by having a red hot poker shoved up his anus, thereby burning his intestines. And I thought politics today was a dirty game....
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Haha those perverted Eurotrash royals make the Windsors today look like model citizens! Dude, that king's death was like Jack Twist in Brokeback or something! Wasn't there some rumor that the brave Crusader Richard the Lionheart was also a homo?
Re: the Plague, yeah that "Guns, Germs, and Steel" book I often hock to you guys does a good job explaining microbial infections and epidemiology in laymen's terms. But Plague was caused by bacteria (BTW, Bubonic Plague bacteria still exist, but are rarely fatal since we have antibiotics and SANITATION now, friggin dirty-ass Euros). HIV is a retrovirus, so it's highly unlikely they have similar lineage or pathways of infection. Actually Plague is fairly similar to E. coli in the bacterial family tree!
I will try not to be a bio geek here, but it's very interesting how microbes jump from one species to another. It's not an easy or quick process. Even scary-ass avian flu only infected humans once (in Vietnam of course), and that incident is under debate. The pathogens tailor themselves over millennia of natural selection (if you believe in that Darwinist crap!) to survive in a certain host, so they need to make special proteins that act as guides to seek out specific cells of a specific species (like HIV only targets human T-cells, while monkey SIV only attacks monkey T-cells). Pathogens also have "cloaking" mechanisms that allow them to escape or reduce immune system defenses. So if we have the flu, we don't pass it to our pets because human influenza only attacks human respiratory cells, and the canine immune system can destroy the virus anyway.
Of course some dangerous pathogens like rabies can infect multiple species, or ones carried in vectors like Plague/malaria have evolved to live in a vector without killing it, then get transported to a host and proliferate there. But for a pathogen to jump species, there has to be hundreds (if not thousands) of years of cross-exposure for the proper mutations to occur. So through thousands of years of fleas living with rats and sucking their blood, the Plague bacteria got into fleas but the host immune system destroyed it. Eventually some strains evolved to be able to live in fleas without generating immune response, and they of course out-competed the dumb Plague that couldn't, and then multiplied. As humans decided to live in unsanitary, densely-populated cities with a lot of garbage/sewage (that attracted rats), all of sudden you have Plague-carrying rats and fleas (with Plague in their blood) in close proximity to people. Once again, human immune defenses cleared the first waves of Plague invaders. But eventually Plague mutated to target human tissues and fend off human immune systems, and the rest is history. Actually Plague kills rats too, so the bacteria gain the added boost that starving fleas are more likely to bite humans once their rat supply wanes.
Actually most (if not all) human pandemics probably came from animals that live closely with us. Scientists know this because the human-attacking forms of the pathogens are genetically similar to pathogens found in domesticated animals. Flu, STDs, malaria, TB, etc. came from fowl, pigs/cows, monkeys, and other farm animals. Talk about revenge for eating them!
Take-home lesson... don't live with trash, excrement, and animals! And D shouldn't have sex with monkeys!
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I was curious about this author's claims, so I check up on it...I think this was the article that the Plague book got the AIDS connection from:
Apparently the genetic "defect" that prevented people from getting the Plague is the same that makes you immune to HIV. It's not exactly an effect of surviving the Bubonic Plague itself since the defective was traced to hundreds of years before the plague.
I agree, the lesson here...don't live in squalor!
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Interesting discussion, thx M! Gives me an excuse not to do work since this is bio-related! I found some more links that strongly support the argument. It does look like Euros were blessed with a mutation that better protected them against HIV (maybe smallpox virus too) versus other peoples. Damn whitey wins again!
There is a mutation on a protein found on immune cells called CCR5delta32. CCR5 is a protein with unknown function in the immune system, probably related to cell motility/recognition during inflammation. Funny I actually studied it a little grad school. So the mutant form is missing some amino acids. HIV uses CCR5 like an anchor to help attach to T-cells and then injects its RNA into the cell to make more viruses. But it seems to have trouble sticking to the "defective" mutant form of CCR5, and therefore it lowers the probability of infection. So I guess not immune completely, but less likely to get sick (since damn resilient HIV can stick to cells via other proteins too). This is what people infer from the data at least.
Beginner genetics here: you know how we have two copies of each gene in our cells? So if we have like 2 copies of "blond hair" gene, we are homozygous blond (and therefore grow blond hair). If we have one blond, one brown gene, we are heterozygous and might have brown hair instead. So people who are CCR5delta32 homozygous have lower HIV infection rates/viral load in blood versus heterozygous, and both are way better than people lacking the mutant ( i.e. most Sub-Saharan Africans). Therefore scientists concluded that CCR5delta32 must be protective against HIV.
It was also implicated in Plague resistance because the incidence of CCR5delta32 spiked a bit in Europe after the Plague versus before (suggesting that Plague killed off more people lacking CCR5delta32). This could just be coincidence though, since the Black Death happened too recently in Euro history to account for the higher incidence of the mutant gene. Between the first plague and the invent of germ theory/sanitation/antibiotics, the pathogen only had 400 years to put "selective pressure" on humans to increase the incidence of the CCR5delta32 gene, which is not enough time. Prevalence of CCR5delta32 only went up 0.8% in the Euro population from 1300-1700 (then it flattened out due to sanitation/medicine). I don't know how they calculated that, probably some fancy math.
Other explanation: CCR5delta32 also happens to protect against smallpox virus, which also sticks to a protein related to CCR5 in order to infect cells. So probably there was a big smallpox epidemic earlier in Europe (2-4 millennia ago), which started the preferrential trend for CCR5delta32. But smallpox has mostly been eradicated since 1980, so CCR5delta32 won't get any more common, except maybe in groups most at risk to HIV. Or CCR5delta32 positive people have to get typed, find each other, and hump a lot to make many babies. Bad news for Africa - since HIV is very recent, Sullivan's model predicts that it would take 1,000 years of HIV pressure to increase the genetic incidence of CCR5delta32 to a protective level on par with Euros (~10-15% of the population).
Heh, apparently Plague first broke out in China, and then spread to Europe via the Silk Road. Good job, Marco Polo! Damn, what epidemic HASN'T started in China!?!
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Like T said, this convo can only go downhill. The Silk Road baby!!! First the plague and then Yao Ming!!!
That's interesting though. Do you think there is anyway for genetists/doctors to use CCR5 to create a vaccine for HIV in the future? It seems like maybe this could be a positive for genetic engineering.
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Haha and I'm sure Yao is carrying a plague or two with him! Only Nate Robinson is immune! Have you guys seen a documentary on that other huge Chinaman Sun Ming Ming? Apparently he has gigantism like Andre the Giant, so his pituitary is on crack due to a brain tumor. I think his docs were able to kill his cancer, but he's just starting to recover now and play some college-level ball. He is very young though and slow/gentle like a sloth, so not sure if he'd survive Shaq or Howard. Dang though, maybe some kurupt docs could implant a tumor by our pituitaries to get us to grow huge, then give us chemo so we don't die. I know Sirc would want to try it!
Well, the tricky thing about CCR5 is that it's already something we have in the body and it probably fills some positive biological purpose on its own. No one has ever tried knocking it out and seeing if we could survive. It would be hard to make that into a therapy though, because somehow you'd have to destroy the normal CCR5 on a person's immune cells, delete the gene that makes new CCR5, and replace it with the protective mutant. We can do this in mice (the technique is called gene knockout, and it won a Nobel), but it's currently unavailable for humans.
Thinking out of the box here, it's possible we could do something like a bone marrow transplant. CCR5 may be found on other cells in our body, but since HIV only attacks immune cells, we only need to worry about those. We could wipe out a patient's immune system (radiation, etc.) and excise all their T-cell-producing bone marrow. But beforehand, we would have taken a bone marrow sample and then performed manipulations to remove the normal CCR5 gene and replace it with CCR5delta32. We can grow up that modified bone marrow culture and re-inject it into the patient, so now he/she will grow immune cells with the protective mutant. All this is easier said than done of course, and will probably cost millions per patient (so forget saving Africa). Also we have to keep the patient in a sterile chamber (like Bubble Boy) while he's waiting for his new marrow, or he'll die of the cold instead of HIV! But heck, Mike Vick can afford it, so after treatment he can bang hos without a Jimmy hat and not worry about HIV! I hope he doesn't sue me if the procedure fails. Theoretically this could work for people who are already HIV positive too. But I'm sure my profs would call me an idiot for even suggesting this. If you're gonna file a patent, gimme a 10% cut or something! One problem though - CCR5 isn't the end-all solution.
Drug companies are already looking at CCR5 as a therapeutic target, but not as a vaccine. It would be for people already HIV positive, just to slow their progression. Since there's no money in a one-shot cure - you gotta string 'em along to get their daily junkie fix like Lipitor or Prozac! So Big Pharmas are trying to develop compounds that stick to CCR5 and block the virus from binding to it (inhibitors). Of course this is not foolproof either, since HIV also attaches to other cell proteins like CXCR4. And the virus is so resourceful: CCR5 is a big protein so drugs can only block a portion of it. HIV can compensate and stick to another area on CCR5 where the drug isn't there. And since HIV is a retrovirus, it mutates much faster than a normal virus like Herpes. So it can adapt and evolve to overcome challenges much faster than our medicine can fight it. If we block CCR5, it may just find another protein to stick to, and possibly become more aggressive in the process (we made it mad), so by trying to cure AIDS we might actually make it deadlier! But it's all speculation at this point, and anything's possible if we try hard enough to fix it. I just don't think there's enough social-political-economic will to save Third World people and homosexuals. And frankly, all this effort is not worth the cost, and it's easier if we can just get people to friggin' get tested and practice safer sex/needles. Again, easier said than done.
New take-home message: basically, we are fucked and microbes will kill us all eventually.
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Forgot to mention, some current therapies only serve to slow viral spread: stop the virus from replicating in the cell, stop the virus from sticking to or penetrating host cells, stop new viruses from breaking out of already infected cells - Tamiflu does this for influenza, etc. This can be effective but not the whole solution. The best would be to help patients eliminate the virus naturally. If we could only "de-stealth" HIV so our immune system can recognize it and kill it better, that would be awesome. For other microbial diseases, drug companies are working on "heat-seeking missiles" like antibodies that specifically and robustly seek out HIV or other targets. Then after they bind, it becomes like a big blip on the radar and our immune cells can then destroy the foreign invader. I guess it's always a safer bet for medicine to help our bodies fix itself, and manipulate nature as little as possible.
Some current strategies in academia and industry involve stimulating the immune system to destroy HIV host cells (so-called CD4/8+ immune cells like T-cells and macrophages), while simultaneously using already FDA-approved antiviral therapy to reduce viral spread. But that is basically analogous to chemo; it's scorched-Earth. If only we could preserve the body and just kill the virus, but that is the billion-dollar challenge.
http://www.aegis.com/pubs/hivplus/1999/jan/cure.html
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