General reply to express thanks for and respond to the several replies my first comment here received. First of all, I wrote in the original reply, "his warnings should be taken seriously," so I am by no means disagreeing with the quoted CDC expert about his general policy recommendations. Indeed, I am on record here on HN[1] saying that I'd like to see the United States follow the lead of the EU immediately in banning antibiotics used in human medicine (especially last-line antibiotics used for antibiotic-resistant human disease) from use on farms. That seems like a sensible way to segregate the ecosystems in which microorganisms develop antibiotic resistance by haphazard evolution through natural selection.
I respectfully note the disagreement of several participants here have with me. They disagree with my disagreement with the interviewed expert's casual language about thoughtful agency by bacteria. Noting your statements that this is just everyday conversational usage, I stand by my objection to that fallacious manner of speaking. Most people in the English-speaking world think erroneously about biological evolution and especially about the implications of evolution for human medicine. I am not alone in thinking that popular thinking about biology needs to be improved by rejecting the idea of organismal agency in evolution,[2] although it is remarkably hard to find this kind of careful thinking by a Google search amid the flood of webpages that specifically assert a purpose or intention to evolution by natural selection. Ernst Mayr, mentioned in one reply to my first comment here, is indeed a rare example of a reliable author on that issue. Human beings have a cognitive bias of attributing agency to inanimate objects,[3] and the reactions to my first comment suggest how deep-seated that cognitive bias is.
The entire revised introduction to the thirtieth anniversary edition of Richard Dawkins's book The Selfish Gene[4] appears to be available for free online reading, and Dawkins writes explicitly about what level of analysis can be useful when pretending that genes have intentions and goals while thinking about problems in evolutionary theory. The University of California Berkeley website about evolution has a good page about antibiotics[5] that makes helpful medical practice and public policy suggestions with more cautious language.
There is a testable prediction here of course: either bacteria outrun human antibiotic development or they do not. I'm confident that more bacterial lineages will be wiped out before human medicine is seriously compromised by natural selection of bacteria that are resistant to most antibiotics used in human medicine. The precautionary principle suggests that we follow the quoted expert's policy recommendations, but meanwhile conduct research for a deeper understanding of the biochemistry of harmful microorganisms and their ecology.
Two other comments at this level express the nub of the argument:
I'm slightly bugged by "desire" type language because it does actually cause problems in how laymen think about evolution. It's not uncommon to hear them make the mistake of thinking evolution will "think ahead". But the bigger problem I have with it is the "anything we do ... bacteria will eventually discover".
Some problems are just very difficult to evolve around, and it's hard to predict what they'll be even if you have a complete working knowledge of an organism's genome and biological workings. If the problem space doesn't contain a solution that can be climbed toward without sacrificing fitness in the short term, it is unlikely that it will ever be found by evolution.
Evolution is actually a really crappy optimization algorithm. The reason it has worked so well is not that it is so effective, but because it's the only game in town.
That is very well put, and deserves your upvote.
At what point do we start designing RNA with a delivery mechanism that attaches itself to a specific bacterial type and eliminates it?
A good question. It is an empirical question about the future, so it has no definite answer yet, but that is the general research direction to follow to get around the legitimate problem mentioned in the article kindly submitted here.
There is a bit of hubris here borne of ignorance. If you study this problem in any depth, you start to appreciate how pernicious it is. I'm not an doctor or epidemiologist, but I learned quite a bit by reading an excellent book[1] on the subject:
> Indeed, I am on record here on HN[1] saying that I'd like to see the United States follow the lead of the EU immediately in banning antibiotics used in human medicine (especially last-line antibiotics used for antibiotic-resistant human disease) from use on farms. That seems like a sensible way to segregate the ecosystems in which microorganisms develop antibiotic resistance by haphazard evolution through natural selection.
Exposure to one agent can make bacteria more resistant to other agents, even ones that are unrelated. This is surprising, but confirmed through experiments. Bacteria have ways of flushing out toxins that become up-regulated, and they become more resistant to toxins in general. Agriculture only uses a few antibiotics, ones that are cheap in bulk, nontoxic to livestock, and can be mixed with feed, but the ramifications could extend to other, more critical, antibiotics used in medicine.
> As we reach a deeper biochemical understanding of the basis of all life, we will eventually understand the differences, which are biochemical differences at bottom, between human beings and bacteria, between human beings and protists, between human beings and fungi (yes, there are some systematic differences between animals and fungi) and between human beings and all other harmful microorganisms.
I think you're underestimating what we already know. Current antibiotics are based on the differences between eukaryotic and prokaryotic cells, and we understand a lot about the underlying biochemistry and drug targets. Lack of fundamental knowledge isn't a primary issue.
> I'm confident that more bacterial lineages will be wiped out before human medicine is seriously compromised by natural selection of bacteria that are resistant to most antibiotics used in human medicine.
Here you're underestimating bacteria. Bacterial lineages don't really go extinct, because they have no well-defined boundaries. Bacteria are very different from eukaryotes and they pick up genes from the environment. See horizontal gene transfer.
This is one of those vicious problems, like cancer, that resists being solved not for lack of our best efforts, but in spite of them.
> "Agriculture only uses a few antibiotics, ones that are cheap in bulk, nontoxic to livestock, and can be mixed with feed..."
The reality is much worse. Factory meat producers will abuse any antibiotic if they are allowed, even the most powerful last-resort antibiotics. For example, many poultry producers were routinely mixing fluoroquinolones into their feed until very recently. The practice was outlawed in 2005, but there is good evidence that some poultry producers continue to do it in violation of the law:
Incidentally, I think the intuitive idea that the last resort antibiotics are the most powerful ones is a bit of a misconception. The ones used as a last resort tend to be the more toxic ones and the ones that have to be given intravenously. The reason they still work is probably because they were used sparingly while there were better alternatives available. That delayed the development of resistance.
> There is a testable prediction here of course: either bacteria outrun human antibiotic development or they do not. I'm confident that more bacterial lineages will be wiped out before human medicine is seriously compromised by natural selection of bacteria that are resistant to most antibiotics used in human medicine.
Do a dumb test. Walk into your nearest hospital, I don't even want to know which it is. Ask how many patients are infected with mRSA. Collect your jaw from the floor when they give you an answer that's 15% if you're lucky, 60-70% if you're unlucky. We have lost the fight with bacteria. It's over. We aren't "about to" lose it, we lost it ~1 year ago, and medicine is fast losing the ability to treat bacterial disease. We lost the fight with viruses a decade ago. If you get infected with a deadly viral disease, like rabies, it's curtains. There's nothing any hospital can do for you except sedate you until you're dead.
We are in fact well on our way to transform hospitals into deathtraps.
> Evolution is actually a really crappy optimization algorithm. The reason it has worked so well is not that it is so effective, but because it's the only game in town.
First of all, the obvious advantage of evolution is it's running time, 3.5 billion years. Second you probably subscribe to the naive notion that evolution, in 3.5 billion years running time, somehow failed to realize that mutation + natural selection is very, very slow. It didn't. The algorithm that, today, controls evolution of pretty much any species works entirely different from what most textbooks teach you. There are very, very few species that evolve through mutation and selection. We evolve through copying of other's genes, simulation and symbiosis (yes, genes can simulate the effect other genes will have on them. Also, most "life" functions of a human body, like breathing, metabolism, ... are actually performed by symbiotic bacteria on our behalf. Human cells can't actually do it themselves).
Unfortunately, if you study how evolution actually works you'll realize what it means for resistant bacteria. Once a fully resistant bacterial strain evolves, a process that takes between decades and centuries, all other species of bacteria will quickly copy the resistance, in a matter of months to years. Which is exactly what we've seen happening.
You'll also quickly realize that no matter how well-intentioned your use of bacteriophages is, it is very, very likely to make things worse, not better.
And the numbers of infections were far lower than you're claiming here - rather than approximately 20,000 in 100,000 as claimed above, the numbers (in 2011) were 4.5 in 100,000.
Yes, MRSA has declined, but not because of improved treatments. Now that we can no longer kill these bugs after they invade the body, hospitals have significantly ramped up their efforts to kill them before they invade.
Hurray for these protocols, but that won't do all that we need. It won't be possible to scrub the whole world with poisons the way we have begun scrubbing hospital rooms. We need ways to stop infections that we can't prevent.
While you're in that hospital, ask what their procedure is if you've been infected with rabies within the past week. It's most certainly not "curtains and sedation."
Just that bit of factual nonsense leads me to believe you are speaking far out of your area of expertise.
Yeah, but after that window closes, our treatment options for rabies are essentially Hail Mary, "Well, it's not like it can get any worse..." level treatments.
That's not a big deal in the U.S. because rabies is quite rare, but in the developing world it's still a thing.
Rabies is a virus - antibiotics don't have any effect on viruses.
Ceol may also be referring to the incubation time for rabies usually being more than a week - if you've just been infected with it and you present at day 7, then a prophylaxis will be administered.
Of which I am well aware, and has absolutely zero to do with the content of my post. Someone disputed that a rabies infection is "curtains" - I posed the circumstances where it is.
You used the wrong term. What's lethal is not "infection" with rabies -- but a full-blown case of rabies.
Rabies infection is very survivable if caught before symptoms start to show up. We have a post-infection vaccine that can be used during the incubation period. We've had a vaccine for over a hundred years, and it works very well. In fact, the original rabies vaccine was the second vaccine ever developed, after smallpox.
What's lethal is symptomatic rabies -- but even that is not 100% lethal. There have actually been a few (under a dozen) documented cases of human survival after symptomatic rabies. Look up the Milwaukee Protocol.
Problem is, the treatment lies within the realm of heroic medicine, works less than 10% of the time, and requires a long period of physical therapy afterwards. The cost easily goes into the seven figures. And we don't even know if the treatment works. Survival might simply be the luck of the genetic draw.
So, $10 million to save the life of one patient with symptomatic rabies, vs. $2000 for the vaccine. So you can see why the treatment protocol emphasizes post-infection vaccination.
When I suggested that there are some "Hail Mary" treatments once the post-exposure prophylaxis window closes, I was talking about the Milwaukee Protocol. Or the, I believe, single reported case of someone surviving a untreated rabies infection with no clear treatment.
As for whether or not I used the right term, I'd actually suggest that "infection" is kind of a fussy term to begin with. But I also never used it in my post, so I'm curious as to how I could have used it wrongly.
I stated that after the treatment window closes for PEP, we're in the realm of very difficult treatments that are really only workable in the developed world. I don't see anywhere that your post and mine are contradictory.
I realize you're probably playing devil's advocate, but there are more issues with the original statement anyway. He implied this was new. Rabies has always been a 100% mortality rate past a certain point in the infection. In addition, he implied that if you're infected, it's game over. It's definitely not. As you've said, there is a window in which you'll most likely be fine with treatment.
Firstly, there's a real difference between rates of MRSA colonisation and rates of MRSA infection, which implies a pathological process at work.
Secondly, what on earth do you mean when you say we lost the fight against viruses a decade ago'?
We have only got better at treating viruses; we had almost no treatment for viruses a decade ago and we have some treatments now; for example we are now much better at treating chronic hepatitis c infection which is a leading cause of liver failure and cancer; we have good HIV drugs which can lead to long term management without significant comorbidities (although many of the pieces were in place a decade ago), and your illustrated case, rabies, has long been a problem child like many significant viral illnesses that are discovered close to the end of their course, has caused so much pathology by tr time they present that the course is terminal.
But there have only been a handful of cases of fulminant rabies in the developed world in the last decade, so it's hardly a thing that we are getting experience in treating.
All the generic virus drugs we had have been eliminted : pretty much all existing viruses are eliminated and we have lost the ability to heal, for example, heal elderly or children infected with the flue (the groups at risk of dying from the disease).
We do not have any drug against any retrovirus (ie. a family of viruses) to which viruses do not show at least partial resistance.
As for the AIDS case, prevention of AIDS has pretty much failed in Africa and the middle east, as well as in significant parts of Asia. It is a matter of a decade or so until ~80% of those populations are HIV positive and the rest of the world will follow in the next few decades. All currently know anti-AIDS drugs will cease being effective in 5 years or less, and the rate of adaptation that the virus exhibits is still accelerating (we wouldn't be able to keep up with the current rate, so sadly, that doesn't even matter).
This is of course assuming we don't have another pandemic like the Spanish flue. We have had several near-pandemic panics in the past decade and all incidents have one thing in common : we failed spectacularly at containment. If, for example, bird flue had been ~6% more infectious than it was, it would have killed ~20% of the world's population (at least), and would have reaped >90% of it's death toll before a vaccine would become available. Absolutely nothing would have stopped it. Bird flue itself was only one of 5 incidents that could have exploded into a pandemic. The big message of these incidents: yes, they stopped, hurray. Sadly it wasn't us who stopped it (but rather small flaws in the virus' design).
There is a staggering amount wrong with this statement. Staggering.
- The prevention of HIV in developing countries is hampered not by the ineffectiveness of drugs, but the expense and difficulty administering them. HIV in the developed world is, in many cases, now essentially a chronic disease. Indeed, it is the use of HAART drugs to prevent transmission in discordant couples that is providing a glimmer of hope for reducing the burden of HIV without a vaccine.
- While serious, prevalence of HIV is nowhere near 80%. Also, increasing prevalence is a function of disease duration, so better treatments will, mathematically, cause prevalence to rise.
- I'd contest rather strongly that we failed spectacularly at containment for several recent outbreaks.
- Antiviral drugs are not our only means of fighting viruses. If "Anti-X drugs" were the solution, we'd have eliminated many bacterial diseases - we haven't. The key to fighting viruses is vaccination, and we've wiped two viruses off the face of the earth, and are largely facing political/social problems, rather than scientific ones, with adding two more to that tally.
>We lost the fight with viruses a decade ago. If you get infected with a deadly viral disease, like rabies, it's curtains. There's nothing any hospital can do for you except sedate you until you're dead.
What? We never had effective antivirals. We have a few useful drugs (oseltamivir, protease inhibitors, etc) for particular viruses, but there has never been a point in human history when rabies was a treatable disease. The Milwaukee protocol, which is the only effective[1] non-vaccine treatment for rabies, isn't even drug-based!
You may of course be confused. The major antiviral used in replications of the Giese case, amantadine, was also an anti-flu drug, resistance to which is now widespread in influenza (see http://en.wikipedia.org/wiki/Amantadine#Veterinary_misuse ). However, I do not believe amantadine resistance has ever been described in rabies, which in any case is usually treated with vaccination -- the challenge is to get the immune system to respond to the virus before the host dies! Giese herself was treated with both amantadine and ribavirin. In any case, your claim is confusing at best, misleading at worst.
Also, most "life" functions of a human body, like breathing, metabolism, ... are actually performed by symbiotic bacteria on our behalf. Human cells can't actually do it themselves
Breathing? Where are the bacteria in the gas-exchange process? And 'metabolism' is a catch-all term that refers to so many different chemical reactions, plenty of which are conducted within the human cells themselves.
He probably confused cellular respiration with physiological respiration, and thus incorrectly conflated the primary purpose of the mitochondria with the physical act of breathing.
"If you get infected with a deadly viral disease, like rabies, it's curtains. There's nothing any hospital can do for you except sedate you until you're dead."
Yeah, but how did we lose that fight a decade ago? Whether or not we'd prefer something better, doesn't the treatment that worked then, still work now?
As another poster has said, we didn't really "lose" that fight. Rabies has always been that way - invariably fatal unless treated, and the only treatment (outside some insane edge cases) is the administration of the rabies vaccine shortly after (or ideally before) contact.
The very low rabies incidence and near zero fatalities of rabies in the developed world actually show that it's a very winnable fight. The issue is, we have to show up to said fight. In the developing world, we're not always good at that.
I hadn't seen the newer revision of the protocol, only the original 2 out of 25 number. "Indistinguishable from 100%" was perhaps a little severe, but 90% survival is still pretty long odds.
> We lost the fight with viruses a decade ago. If you get infected with a deadly viral disease, like rabies, it's curtains. There's nothing any hospital can do for you except sedate you until you're dead.
The fight we have not yet one is the fight against poverty.
Not many wealthy people die of rabies.
AIDS which was once fatal, is no longer, provided you can afford the treatment.
Honestly, at this point HAART treatments for HIV are giving folks a near natural lifespan, and the major threats to their health are becoming diseases of old age - cancer and the like. And the years they have are fully functional.
Compared to a chronic, wasting disease that will take years of opportunistic infections before you die, that's damned good.
Magic Johnson and Andrew Sullivan have had HIV for over 20 years and seem to be handling it fairly well. Certainly a harder life than most, but that's not stopping them from living a full life.
Let me do what I hope will be a smart test here by sharing some more information and asking some follow-up questions. I invite onlookers to comment about this too.
The Centers for Disease Control and Prevention (the same organization that employs the expert quoted in the article submitted to open this thread) reports that "Although MRSA is still a major patient threat, a CDC published in the Journal of the American Medical Association Internal Medicine showed that invasive (life-threatening) MRSA infections in healthcare settings are declining. Invasive MRSA infections that began in hospitals declined 54% between 2005 and 2011, with 30,800 fewer severe MRS infections. In addition, the study showed 9,000 fewer deaths in hospital patients in 2005 versus 2011."[1] So there are responses already in place that are gaining on antibiotic-resistant bacteria in hospital settings in the United States.
I care about the spread of antibiotic-resistant bacteria. I am gravely concerned about the medical and public-health practices in India that have resulted in a massive increase in patients infected there with multiple-antibiotic-resistant tuberculosis.[2] I am 100 percent behind the idea that antibiotics have to be used cautiously and responsibly, and meanwhile we have to keep researching other means of infection control besides antibiotics.
You wrote,
We evolve through copying of other's genes, simulation and symbiosis (yes, genes can simulate the effect other genes will have on them.
Do you really mean "we" there? Are you saying that this mechanism in any way makes it impossible for human beings to eradicate harmful microorganisms? How? Please connect the dots to back up your conclusion that
Once a fully resistant bacterial strain evolves, a process that takes between decades and centuries, all other species of bacteria will quickly copy the resistance, in a matter of months to years
because the "all" there and the time scale you talk about both appear to be exaggerations, especially in light of the progress that has already occurred in limiting MRSA infections in the United States.
>Unfortunately, if you study how evolution actually works you'll realize what it means for resistant bacteria. Once a fully resistant bacterial strain evolves, a process that takes between decades and centuries, all other species of bacteria will quickly copy the resistance, in a matter of months to years. Which is exactly what we've seen happening.
This is the important point that people forget. Bacteria are experiencing an extremely accelerated time course and can evolve and exchange advantageous mutations very quickly. We have only had antibiotics for 100 years, which is 3-4 generations of man, but billions of generations of bacteria!
I am not actually sure that it takes as long as people think. The fact is it isn't just individual genes, but selection for combinations of them. If you look at random mutations, I think that is likely dwarfed by random permutations. This is why the resistance bell curve shifts over time. You aren't just selecting for a single gene, but for a function, which could be carried out any number of different ways, and which any number of different gene combinations could do it.
I respectfully note the disagreement of several participants here have with me. They disagree with my disagreement with the interviewed expert's casual language about thoughtful agency by bacteria. Noting your statements that this is just everyday conversational usage, I stand by my objection to that fallacious manner of speaking. Most people in the English-speaking world think erroneously about biological evolution and especially about the implications of evolution for human medicine. I am not alone in thinking that popular thinking about biology needs to be improved by rejecting the idea of organismal agency in evolution,[2] although it is remarkably hard to find this kind of careful thinking by a Google search amid the flood of webpages that specifically assert a purpose or intention to evolution by natural selection. Ernst Mayr, mentioned in one reply to my first comment here, is indeed a rare example of a reliable author on that issue. Human beings have a cognitive bias of attributing agency to inanimate objects,[3] and the reactions to my first comment suggest how deep-seated that cognitive bias is.
The entire revised introduction to the thirtieth anniversary edition of Richard Dawkins's book The Selfish Gene[4] appears to be available for free online reading, and Dawkins writes explicitly about what level of analysis can be useful when pretending that genes have intentions and goals while thinking about problems in evolutionary theory. The University of California Berkeley website about evolution has a good page about antibiotics[5] that makes helpful medical practice and public policy suggestions with more cautious language.
There is a testable prediction here of course: either bacteria outrun human antibiotic development or they do not. I'm confident that more bacterial lineages will be wiped out before human medicine is seriously compromised by natural selection of bacteria that are resistant to most antibiotics used in human medicine. The precautionary principle suggests that we follow the quoted expert's policy recommendations, but meanwhile conduct research for a deeper understanding of the biochemistry of harmful microorganisms and their ecology.
[1] https://news.ycombinator.com/item?id=5674781
[2] http://whyevolutionistrue.wordpress.com/2011/02/21/natural-s...
[3] http://cogsci.stackexchange.com/questions/3951/is-there-a-co...
[4] http://books.google.com/books?id=koaD_Aod_V0C&printsec=front...
[5] http://evolution.berkeley.edu/evolibrary/article/medicine_03
Two other comments at this level express the nub of the argument:
I'm slightly bugged by "desire" type language because it does actually cause problems in how laymen think about evolution. It's not uncommon to hear them make the mistake of thinking evolution will "think ahead". But the bigger problem I have with it is the "anything we do ... bacteria will eventually discover".
Some problems are just very difficult to evolve around, and it's hard to predict what they'll be even if you have a complete working knowledge of an organism's genome and biological workings. If the problem space doesn't contain a solution that can be climbed toward without sacrificing fitness in the short term, it is unlikely that it will ever be found by evolution.
Evolution is actually a really crappy optimization algorithm. The reason it has worked so well is not that it is so effective, but because it's the only game in town.
That is very well put, and deserves your upvote.
At what point do we start designing RNA with a delivery mechanism that attaches itself to a specific bacterial type and eliminates it?
A good question. It is an empirical question about the future, so it has no definite answer yet, but that is the general research direction to follow to get around the legitimate problem mentioned in the article kindly submitted here.