Injustice even at the roof of the world

http://m.newyorker.com/online/blogs/newsdesk/2014/04/everest-sherpas-death-and-anger.html?utm_source=tny&utm_campaign=generalsocial&utm_medium=facebook&mbid=social_facebook

http://www.npr.org/2014/04/18/304574129/disaster-on-everest-marks-deadliest-day-in-mountains-history

Maybe you heard about the deadliest day in Everest history. Most people understand that climbing is very risky no matter what, but a recent trend has been shifting the danger from the high-paying Western customers ($50-90K per person) to the staff of sherpas that climbing org's employ to "set the table" for the customers. These sherpas (lowercase "s" for the profession, uppercase "S" for the ethnic group that represent the vast majority of sherpas) are paid $2-8K per expedition, with a death insurance of $10.5K to their families. So you can see where the majority of the profits go.

It's not just financials, but the climbing experience too. Sherpas have to traverse the more hazardous portions of Everest dozens of times (maybe even 30) for every one pass from a paying customer. They haul gear back and forth, set up acclimation camps, and lay down ropes and ladders. The most dangerous stuff that is usually core to climbing. Now the paying customers just pack water and a camera, literally. Not surprisingly, western death rates on the mountain have plummeted in the last 20 years, but guess who is picking up the slack? Some of this is due to better use of canned oxygen and dexamethasone (a drug that makes edema less likely). But O2 is heavy - guess who hauls the cans up and down for the customers? And most sherpas do not have modern medical care, so they don't get dex in their villages and their employers don't seem to want to buy it for them.

Understandably, the sherpas have threatened to strike unless climbing org's and the Nepalese gov't give them better safety protection and family benefits. This is coming from a traditionally stoic people. It would be like if the Hulk tells Capt. America that he is worried about the next mission - you better freaking pay attention.

The "outsourcing" of risk and concentration of profits stink of the negative side of globalization. Of course the top climbing org's are exclusively foreign-owned. Yes the sherpas are paid better than their next best available employment alternative, but it is not worth a job that is many times more dangerous than being a soldier in Iraq, statistically. And remember, Blackwater contractors got six-fig salaries and hazard bonuses at the expense of the US taxpayer, just to cook or drive a truck.

I thought the whole point of climbing a mountain was to prove your mettle? It is you and the rock, not you + an army of support staff because you can afford it. Of course for such a challenge as Everest, it is a team effort, but this is not right IMO. Is this just another way for big shot 1%ers to have a story to tell and show how badass they are? But in reality, they are only doing about 1% of the work needed to climb and survive Everest - at the expense of many local deaths. Hey, no one wants to die - I get that. But then don't climb freaking Everest; play a round at Pebble. They want their cake and eat it too, like most everything else in their amazing lives. And it doesn't matter about the consequences to others. They get what they want because they earned it and deserve it, just like Romney said.

I hope the sherpa strike works out, and they get at least 75% of the available profits from expeditions. Because they are the key resource (like the student athletes vs. the NCAA). Any schmuck can manage the front desk, assuming zero risk. And maybe the sherpas will let Joe Wall St. haul his own damn tent and tanks next time, if he is such a Master of the Universe.

A humane and intelligent approach to end-of-life medical care

This interview with physician Sherwin Nuland was very thoughtful and IMO is a prudent approach to the uncomfortable subject of managing end-of-life care decisions. I know medicine and death are very personal and emotional subjects, but I think if we dispassionately put the patient's best interests first and keep expectations reasonable, everyone will end up happier (especially the deceased) and society can save a lot of health care resources.

One issue that the doc didn't cover in the interview was assisted suicide, which has few rational arguments against it, and is becoming more accepted nationwide - similar to legal pot and gay marriage.

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Also heard something about end-of-life care on NPR the other day.  There was a particular city that had a big promotion of advanced medical directives.  What they found was that, as a result, medical costs went down quite a bit in their city.  Apparently when people make a positive choice about the type of life they consider worth living it is significantly less expensive than the care legally mandated in the absence of a positive choice.

The major roadblock to those advanced directives is human effort and human emotion.  Understandable and probably not an incredibly high hurdle to overcome.

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Agreed. More and more people are preferring to die relatively peacefully at home or hospice rather than "keep fighting" to the end with all the tubes and drugs in them at County General. And the irony is that the former group tends to last longer, and with less grief on themselves and the family, than the latter (obviously at much lower cost too as you said).

There are plenty of war stories where the stubborn commander refused to face reality and sentenced himself and his men to preventable death. Even worse, a stupid, egomaniac dictator doesn't understand opportunity cost, ignores his generals' pleas, and keeps throwing finite resources at an unwinnable battle, which ironically contributes to losing the overall war - see Stalingrad or Guadalcanal. We tend to mock those men and use their folly as teachable moments. So why can't we apply the same logic to medicine? Unfortunately there is such a thing as a no-win scenario, so the sooner we come to terms with that, the better it is for everyone. Would you gamble your life savings on 1 play at 1/1000 odds at the casino? Of course not - so why do we do it at the hospital? Is it because of moral hazard, or the finality/unknown nature of death?

On a personal note, what I really hate to see are relatives pressuring the dying person to "keep fighting" and "not let the disease win". It gives the false impression that the outcome is mostly in the patient's control, and it's a matter of effort/will. The patient has enough to worry about without that guilt. No one wants to be reminded that they are the source of the everyone's sadness, like it's their fault. Families may bring up outliers like Lance Armstrong, but forget that 99.99% of folks like Lance didn't make it. I'm not saying to abandon all hope, but at least don't impose ludicrous expectations. Unfortunately, the next of kin can get pretty selfish and they may not be ready to let go. But during these tough times, the best thing they can do is show as much comfort and compassion as possible for the dying.

But if it's the patient insisting on exhausting every medical possibility no matter the odds or costs, I am not sure how a physician or relative can/should dissuade them respectfully. 

More on prescription drugs

Yeah, for a culture that's so gung-ho about wars on drugs, just saying no to drugs, etc. there sure is a lot of accommodation of prescription drugs; yet another mystery of American life, eh?

BTW, I did want to add one thing to the discussion (top-posted per request, cross-posted with T's Blogger Blog, & duplicated to Google Groups for posterity): it could be that the real villain with respect to over-prescription of drugs is actually the privacy policies which make data collection regarding drug interaction as well as long-term efficacy something of a question rather than a no-brainer... I know that there are plenty of systems (and algorithms) which are capable of automatic collection and anonymization of such data so the technology definitely exists; as far as I'm know the only reason such systems haven't been deployed (or federated) is a lack of will and/or legal framework to allow the needful to be done.

PS: DTC marketing is obnoxious and more existential than hanging out at a gym; it's reason enough to turn off the TV for good and/or abandon network television for good.

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Thanks for writing. Yeah Rx painkillers are I think in the top 5 for illicit drug abuse in America. But instead of brown people smuggling blow across the Rio Grande to poison our kids, American drug pushers just have to raid grandma's medicine cabinet or obtain a bogus Rx. I am sure most of you have heard stories of even teens selling their leftover vicodin to classmates after a wisdom teeth removal or whatnot. Customer service is generally pretty poor at most retirement homes and hospice care centers for the sub-rich, but one thing they're great at is medicating the elderly. Then they have to deal with fewer complaints and whining.

Another problem is how to dispose of all the surplus drugs. It's fairly well documented that doctors overprescribe antibiotics for even viral illnesses or patients whose symptoms are not severe (and would probably recover on their own, but the doc wants to be careful and not upset the patient/get sued). This selective pressure gives an evolutionary advantage to drug-resistant bacteria strains. Discarded antibiotics and other drugs are winding up in our water supply. Our water purity tools are now more sensitive, so maybe drugs were always there and now we can finally detect them, but still - it's quite likely that we're ingesting trace amounts of all sorts of drug cocktails when we drink tap water (or even cheap bottled water).

http://www.staphaseptic.com/news.cfm?id=18FE4C5D-C6C9-0EF9-9F1678797221DAA9
http://www.usatoday.com/news/nation/2008-03-10-drugs-tap-water_N.htm

As you said, there isn't much data on long-term drug effects, drug interaction, or even acute side effects. With pressure from drug companies and even overzealous patient advocacy groups to get products to market ASAP, the FDA is unable to be totally thorough. There is a new prostate cancer vaccine (Provenge) being reviewed by the FDA. 4/17 docs on the advisory panel have concerns about the drug's efficacy, and two published their findings. The authors now need 24/7 bodyguards because crazy people are making death threats to them, because they think the docs' obstruction is threatening theirs. Even though the docs are doing this out of concerns for potential patients and have no financial incentive, unlike other docs who praise drugs from companies that do them favors. This is the state of medicine today.

http://www.psa-rising.com/blog/2007/06/prostate-cancer-doctor-receives-death-threat-over-provenge/

As we know, haste causes mistakes, like in the cases of Vioxx, Raplon, Palladone, Trasylol, Baycol, Raptiva, or other drugs that were initially approved and pulled after drug-related deaths/complications were reported. Just do a Google search for "drugs pulled from market" and you will find a huge list. The FDA, NIH, and other gov't entities are underfunded and understaffed. In fact, most drug testing is funded and conducted by the company itself, and the FDA just reviews their paperwork. Or resources are poorly allocated: breast cancer research gets the most funding (30% of all NCI grant funding), even though it is not the most common nor lethal cancer, probably due to America's Oedipal fixation with mammaries and maternal guilt issues. But long-term studies are expensive and time-consuming, and it's hard to follow patients for years. We hope academics will conduct these critical studies for us, but they have their own constraints and there's still so much we don't know. Maybe with more electronic records, information sharing, and sophisticated computational methods, we can learn more about the pharmacokinetics/dynamics of various drugs, but as you would expect, the medical field is not at the cutting edge with respect to computing. As you said, without the gov't will and legal mandate to obtain these data, it will never happen on its own.

http://www.cancer.gov/cancertopics/factsheet/NCI/research-funding

Attitude-wise, I think patients should stop expecting new miracle drugs to keep curing them of illnesses and improving/extending their lives. Practically everything out there is a carcinogen or pathogen. Maybe diseases evolve faster than science (and bureaucracy) can combat them anyway. The "George Bush approach" that technology will always save us from ourselves is not valid in most cases, and probably foolhardy. Yes we should rationally and ethically continue research and try to help the sick get better, and yes drug companies and doctors deserve reasonable compensation for the products/services they provide, but let's remember that we are all mortal and fragile. Death is part of life, and let's face it with some zen and humility. Why are you so important that society needs to spend half a million dollars so you can see your 86th birthday? Research isn't really the problem either. The top killers in the world are respiratory complications (from flu, pneumonia, etc.), tuberculosis, and malaria. All those are easily and CHEAPLY preventable/treatable. But of course the people who die from them are from the Third World, and we don't give a shit about them. The top killers in the West are probably heart disease and cancer. So we pour billions of dollars into research and care for those diseases. Probably one infusion of chemotherapy ($10k in some cases) could pay for an entire village's anti-malarials for a year.

Black death, HIV, and CCR5

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?

http://www.greenwood.com/catalog/GWP002.aspx

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!

http://www.cdc.gov/ncidod/dvbid/plague/

http://www.themiddleages.net/plague.html

http://www.cdc.gov/hiv/resources/qa/qa3.htm

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:

http://findarticles.com/p/articles/mi_m1589/is_2002_Oct_29/ai_94079748

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!

http://www.chinadaily.com.cn/sports/2006-10/09/content_703642.htm

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.

http://en.wikipedia.org/wiki/CCR5

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/immune.html

http://www.aegis.com/pubs/hivplus/1999/jan/cure.html