Didn’t see that one coming »« MOOCs don’t work?

Chilling

That’s all I need, another reason to cower at home in terror of the perils of the real world. Maryn McKenna imagines our Post-Antibiotic Future, that time when bacteria have more thoroughly evolved to resist our medicines — and you’ll be frightened after you read it, too.

Before antibiotics, five women died out of every 1,000 who gave birth. One out of nine people who got a skin infection died, even from something as simple as a scrape or an insect bite. Three out of ten people who contracted pneumonia died from it. Ear infections caused deafness; sore throats were followed by heart failure. In a post-antibiotic era, would you mess around with power tools? Let your kid climb a tree? Have another child?

“Right now, if you want to be a sharp-looking hipster and get a tattoo, you’re not putting your life on the line,” says the CDC’s Bell. “Botox injections, liposuction, those become possibly life-threatening. Even driving to work: We rely on antibiotics to make a major accident something we can get through, as opposed to a death sentence.”

Bell’s prediction is a hypothesis for now—but infections that resist even powerful antibiotics have already entered everyday life. Dozens of college and pro athletes, most recently Lawrence Tynes of the Tampa Bay Buccaneers, have lost playing time or entire seasons to infections with drug-resistant staph, MRSA. Girls who sought permanent-makeup tattoos have lost their eyebrows after getting infections. Last year, three members of a Maryland family — an elderly woman and two adult children — died of resistant pneumonia that took hold after simple cases of flu.

She does offer some slight hope for the future.

What might hold off the apocalypse, for a while, is more antibiotics—but first pharmaceutical companies will have to be lured back into a marketplace they already deemed unrewarding. The need for new compounds could force the federal government to create drug-development incentives: patent extensions, for instance, or changes in the requirements for clinical trials. But whenever drug research revives, achieving a new compound takes at least 10 years from concept to drugstore shelf. There will be no new drug to solve the problem soon—and given the relentlessness of bacterial evolution, none that can solve the problem forever. In the meantime, the medical industry is reviving the old-fashioned solution of rigorous hospital cleaning, and also trying new ideas: building automatic scrutiny of prescriptions into computerized medical records, and developing rapid tests to ensure the drugs aren’t prescribed when they are not needed. The threat of the end of antibiotics might even impel a reconsideration of phages, the individually brewed cocktails of viruses that were a mainstay of Soviet Union medical care during the Cold War. So far, the FDA has allowed them into the U.S. market only as food-safety preparations, not as treatments for infections.

MORE SCIENCE. MUCH MORE.

Comments

  1. Friendly says

    Can we please incentivize continuing research into phage therapy as well as antibiotics? It’s a lot harder for bacteria to adapt to attacking parasites than it is for them to adapt to passive chemicals.

  2. moarscienceplz says

    How about a tax on all those annoying drug commercials to fund a NIH antibiotics program? I don’t trust big pharma to actually focus on the best products. They’d more likely try to tweak an existing product just enough to claim a new patent rather than develop something new.

  3. says

    When the first antibiotic was discovered, we knew that they would be a temporary measure. I think phages would be a useful tool, but they have to be concocted ad hoc and designed to fit a specific infection: they are not a general use weapon that can be ordered in bulk and sit on a shelf until needed.

    It will definitely be a different world from what we’ve become accustomed to.

  4. carlie says

    PHAGES, FOR FUCK’S SAKE. What will it take to get over the psychological hump of “if Communists developed it, it must be bad”?

  5. says

    Maryn McKenna has been banging that drum without many people listening for a long time. I’m glad people are starting to take her (and others like her) more seriously.

    First thing we have to do is to severely limit/eliminate the use of antibiotics on animals. At most, it should be allowed for only highly infectious bugs, and NEVER to promote growth. That’s practically genocidally greedystupid, and the US ag industry in particular is doing so in insane amounts. That would take a hell of a lot of evolutionary pressure off the process, and give us a chance to start a crash program to develop more, prontissimo.

    What we’ll actually do, of course, is basically nothing until a huge infection wipes out most of a city.

    Well, when one wipes out the white areas of a city, anyway.

  6. raven says

    Yeah, we are on the Darwinian treadmill with antibiotics, antivirals, herbicides, insecticides, anti-everthings. And don’t know how to get off.

    A local ER doc had a healthy 20 something come in with bronchitis. Gave him a broad spectrum antibiotic and told him to come in if it didn’t work or a week, whatever happened first.

    He didn’t show up. They had the police do a welfare check. He was dead, pneumonia. WTH, this isn’t supposed to happen and not that fast. Best guess is he came down with a multidrug resistant superbug of some sort.

    There is a new strain of TB, XDR-TB, resistant to all antibiotics. In one patient series, with treatment, mortality was over 90%.

  7. raven says

    PHAGES, FOR FUCK’S SAKE. What will it take to get over the psychological hump of “if Communists developed it, it must be bad”?

    It’s not that simple. For one thing, they didn’t. That idea of magic arrows has been around since phages were discovered.

    The idea is old, its been tried many times, and for various reasons hasn’t worked well. Problems with delivery, problems with half life, problems with access. Your phages aren’t going to work well if the bacteria are intracellular or in an abcess.

  8. says

    Hmm. It would be complicated, and maybe not practical, but one solution would be to take penicillids (and engineer some to not be toxic to some part of the population), and find a way to expose them to markers on viruses. Basically, add in factors to their genes that “react” to the presence of the virus you want to kill, like surface markers for it, by actually harming the penicillid in some way, then fight fire with fire – the virus killer would need to adapt a way to kill the new strain, by modifying its own toxins. Right?

    I mean, if you are going to use antibiotics at all, you need them to be adaptive, like the thing they are killing, not just, “Lets throw a chemical at the thing and hope it doesn’t mutate too fast.”

    But, yeah..

  9. unnullifier says

    [...]
    The need for new compounds could force the federal government to create drug-development incentives: patent extensions, for instance, [...]

    I really hope that this (patent extensions) doesn’t happen. I don’t understand why many people I find respectable and intelligent seem to consider patents a good incentive method and measure of innovation. It’s nether: if there are patent extensions on drugs / antibiotics then pharma corporations will have more of an incentive to sit on their hands until their patent expires. Once it does expire what usually happens is that pharma companies make a very small or worthless change to the chemical compound in their drug and re-patent it. That’s kind of the opposite of innovation.

    Removing pharma patents entirely would actually force more innovation, since pharma companies would no longer be able to afford to rest on their previous efforts and competitors would spring up all over the place.

  10. Chie Satonaka says

    You’d think that considering that fact that every person needs antibiotics and that corporate farms are buying a shitload of them that there would actually be money in developing new ones.

  11. wpjoe says

    There needs to be more incentives for drug companies to make/find antibiotics. Since people will only take antibiotics for a week or two, the drug companies have more incentive to make drugs you will take every day forever (like antidepressants, ERD drugs, etc) than antibiotics. If there were an X-prize or big contracts for a sufficiently long time to get through all the discovery and testing phases, then it might make sense. Currently, it is fiscally risky for drug companies to attempt to develop antibiotics.

  12. billgascoyne says

    Pardon my biological ignorance, but how long might it be (if ever) before the resistant bugs “forget” how to resist the old antibiotics, and these become effective again?

  13. brett says

    @13 billgascoyne

    It’s hard to say, although I’ve read that the kind of widespread resistance that you see in some strains of bacteria tends to have a steep “cost” in terms of evolutionary fitness. Take away the not-so-careful dosing of antibiotics, and vulnerable strains might out-breed them again.

    There have been a few efforts that worked to get resistant strains under control. Israel really got CRE infections down in its hospital system, for example. But we need to go beyond that, and ban the widespread dosing of livestock with antibiotics, and also put more constraints on their prescription at the local GP level. That would at least help to curb domestic outbreaks, although there’s still a risk that a resistant strain could be brought over from a third world country with bad/inadequate practices on antibiotics use (read: India).

    @10 nullifier

    Removing pharma patents entirely would actually force more innovation, since pharma companies would no longer be able to afford to rest on their previous efforts and competitors would spring up all over the place.

    That would just kill new efforts. You’d have the drugs already far along enough in the pipeline finished up, but then a complete drop-off after that.

    As for the practice you mentioned, it’s exaggerated – and a lot of the “minor changes” are small improvements that add up over time, or new ways of getting to the same outcome (which matter – you want more than one way to treat a disease in case someone has an allergic reaction to the main drug used to treat it).

    What you need is some way to defray some of the brutal costs involved in running large-scale clinical trials. That would not only help to lower the cost of developing new drugs, but it would also allow for more duplication studies to determine how effective they are.

  14. says

    @carlie #4 – Phages are useful, in that we can breed/engineer different viruses to attack new and evolving bacteria. They are not, however, a general use weapon: a phage that can destroy A will be useless against B, and different strains of C may each require different phages. Every dose of phage therapy would have to be mixed to order in accordance with the very specific infection or combination of infections, which means taking time to find out what, exactly, the patient has. And because phages are viruses, there is always a chance that a phage will turn rogue and end up doing damage to the person, either by killing off essential symbiotic bacteria or by mutating to where it can infect human cells.

    Bacteriophages do solve a lot of the problems that come with antibiotics, but they introduce a whole host of other problems.

  15. raven says

    You’d think that considering that fact that every person needs antibiotics and that corporate farms are buying a shitload of them that there would actually be money in developing new ones.

    There is a big market now. As long as there was a collection of cheap, effective antibiotics, no one thought more was needed. Besides which, for various and largely unknown reasons, finding new antibiotics became very difficult.

    1. The suits that run big pharmaceutical companies can be really stupid. Not all of them but many.

    2. We once presented a project to a multinational. Reply. “Cancer doesn’t make money.” Which was the conventional mantra and half right at that time. This was right before biologicals and targeteds hit. The truth is, cancer drugs that work make tens of billions of dollars.

    3. Same thing with anti-HIV AIDS drugs. One suit said AIDS, who cares. It’s not like an arthritis or cholesteral drug, small market. Then the HIV epidemic took off worldwide. The reality is, it was a huge market and there are dozens of anti-HIV drugs.

  16. says

    Brett @ 14:

    But we need to go beyond that, and ban the widespread dosing of livestock with antibiotics, and also put more constraints on their prescription at the local GP level.

    This, this, this. I eat very little meat, but what I do eat wasn’t subjected to antibiotics. I do have the luxury of buying from farms I can check out in person, and from people I know.

    When I read this, I was trying to remember the last time I took antibiotics. Somewhere in the neighbourhood of 11, 12 years ago, for a cat bite.

  17. raven says

    Pardon my biological ignorance, but how long might it be (if ever) before the resistant bugs “forget” how to resist the old antibiotics, and these become effective again?

    Everyone wonders about that. It’s an important question and a fond hope.

    1. I wouldn’t count on it though. In Africa, they stopped using the old malaria drugs because they did nothing.

    The malaria strains lost their resistance. So someone tried the old drugs. The resistant strains quickly came back. Once the drug resistance evolved, it didn’t disappear completely. And as soon as selection was applied, it came back.

  18. Pierce R. Butler says

    When a Minnesotan says, “Chilling”, the rest of us should interpret that as, “Would make a cubic kilometer of nitrogen ice shiver.”

  19. ryanb says

    Perhaps it’s the godless socialist in me but what’s with all the focus on markets and incentives for big business? Why not fund the research directly with government grants, including clinical trials, and then produce whatever works at the cheapest possible cost in publicly owned pharmaceutical factories? There’s no need for just one country to do this, it could be an international effort.

    Oh wait I know, because this way people wouldn’t be able to make excessive personal wealth at the expense of the health of fellow humans. Silly me for forgetting that.

  20. carlie says

    Eliminating constant use of antibiotics in agriculture would go a long, long way. It needs to be done. As for the question of how quickly they regain susceptibility, it is being studied (source); it can happen pretty quickly, but a lot of factors are involved. There have been a few splashy studies where rates of infection plummeted within the year or so after restrictions on antibiotic use in a single hospital were put in place one example ). But there’s still a lot of low-hanging fruit; compliance on things like fucking washing hands between patients is still not where it should be ( example ).

    There are more ways to fight antibiotic-resistant bacteria than developing more antibiotics, we know what they are, and we’re shit at doing them, in part because they involve behaviors that are tedious and annoying rather than being something that can be profited from.

  21. carlie says

    The abiotic transmission route of bacterial spread is a big area that can be attacked – when they’re forced to go human-human transmission only, they start to evolve less virulence. summary source.

  22. alt3 says

    This is why I don’t use doctors. Now when we’re knocked back to the nineteenth century, medicine-wise, I’ll already be used to it.

  23. says

    Once it does expire what usually happens is that pharma companies make a very small or worthless change to the chemical compound in their drug and re-patent it. That’s kind of the opposite of innovation.

    Or, they dump the product to smaller manufacturers, since its now, “A lot profit per volume item, and not worth it to produce.” There are a lot of “critical” medications in that category, many of which run into shortages, or contamination issues (or due to those), all the time, because “big pharma” doesn’t want to be bothered selling things that cost a few cents a pill, instead of the newest, and greatest, $500 a bottle product.

  24. davem says

    I’m half way through a six week course of antibiotics, consuming a pack every two days,. That’s 21 packs of 24 tablets. Someone must be making a profit, surely?

  25. says

    Some of the worst problem bugs we see here in Australia have come to us via India and Pakistan, where you can still buy antibiotics like lollies over the counter.

    On top of that we have a C difficile epidemic, and low vaccination rates (and what we suspect are antigen changes in eg bordetella pertussis) are bringing back long forgotten infections.

    In hospital we are now limiting the everyday use of certain potent broadspectrum ABx by requiring ID approval, and are generally trying to rationalise our antibiotic use more.

    But it’s a challenge.

  26. carlie says

    rorschach – and patient pressure has to be huge. Trying to give someone a crash course in evolution, bacterial life history traits, and antibiotics while they’re looking at their child/parent/spouse suffering RIGHT NOW AND WANTS IT FIXED has to be extraordinarily difficult.

  27. says

    I don’t remember where I read it (Respectful Insolence?), but I recall hearing that introducing resistant bacteria to two antibiotics that counteract each other tends to breed non-resistant bacteria. I think it’s because having raw efficiency ends up benefiting the bacteria more than having the resistance.

    I’m not sure if that tactic can be applied at all effectively, since it only affects the bacteria in whatever’s being treated, not the wild population as a whole. Even if a patient survives the infection long enough for the bacteria to shed their resistance, there’d likely still be lingering resistant bacteria that can survive after the new non-resistant ones get treated, putting the problem back at square one. It might work if the technique replaced the mass antibiotics in livestock, but it wouldn’t be easy to convince the people raising the livestock.

  28. brett says

    @22 ryanb

    Perhaps it’s the godless socialist in me but what’s with all the focus on markets and incentives for big business? Why not fund the research directly with government grants, including clinical trials, and then produce whatever works at the cheapest possible cost in publicly owned pharmaceutical factories? There’s no need for just one country to do this, it could be an international effort.

    What makes you think it would be cheaper to do that? On top of that, which drug research priorities you pursue are now much more heavily politicized as opposed to the prior system, where drugs get research money as long as the company thinks they stand a chance of making a profit on the discovered drug. Who decides which drugs get money for research and clinical trials?

    We know what a fully socialized health research set-up looks like, from the Soviet Bloc countries. It was not a source of great medical innovation, unless you want to count biological warfare.

    @23. Carlie

    There have been a few splashy studies where rates of infection plummeted within the year or so after restrictions on antibiotic use in a single hospital were put in place one example ). But there’s still a lot of low-hanging fruit; compliance on things like fucking washing hands between patients is still not where it should be ( example ).

    That’s good to hear. And yeah, the hand-washing rate (even in hospitals!) is deplorably low.

  29. rowanvt says

    Our pets are also a vector. One of my teachers at tech school told a story about her days as a vet student. Living on campus in one of the wards was a beagle with chronic UTIs. The students dealt with her rather than the instructors. The instructors, in fact, were mostly ignorant of her recurrent problems. Then my teacher decided to get to the bottom of doggy’s problem and cultured her urine, using the standard protocols to find out which antibiotic the organism was susceptible to.

    The bacteria was immune to EVERYTHING.

    She immediately brought the results to her teachers who did some digging into the situation, and also immediately euthanised the beagle. The other students, past and present, had been aware the dog was resistant to everything and had deliberately hidden this fact from their instructors. This dog was also allowed to greet visitors.

    They were lucky, but if the wrong person had said “hi” to this dog, they could have died.

  30. voidhawk says

    I was mugged a few years ago and the attackers knocked out my two front teeth. An abscess developed in the root of one of the broken teeth. It’s scary to think that a relatively minor inconvenience needing some cosmetic work and a round of antibiotics now was once a death sentence and could be again if we don’t get cracking on solving this problem.

    Killed by a punch to the face over a crappy mobile phone, not exactly the way I’d want to go.

  31. Stacy says

    @ryanb #22

    Perhaps it’s the godless socialist in me but what’s with all the focus on markets and incentives for big business?

    I’m with you. The main reason we’re in this mess is that antibiotic R&D isn’t profitable.

    We’ve seen this coming for years. But profit uber alles, until we reach the point where those with access to the best in health care can no longer ignore the problem.

  32. Amphiox says

    Yeah, we are on the Darwinian treadmill….

    No one and nothing ever gets off the Darwinian treadmill. Fundamental law of biology and all that.

  33. M can help you with that. says

    Brett @ 21 —

    So, instead, we’re supposed to shovel money (and free giveaways of the results of publically-funded research) to companies that have decided that the best return on investment is to prioritize convenience drugs for the wealthy over the survival of everyone else? More dollars and lives burned as sacrifices on the altar of the invisible hand?

  34. lorn says

    IMHO the failure of antibiotics is an essentially a private enterprise failure. The first antibiotics were either given away by researches for the public good or some mix of private/public research dollars. The overuse and inappropriate uses have been overwhelmingly undertaken for the benefit of private profit.

    Presently every branch of the military has some sort of chemical/bio-weapons specialty and most maintain some sort of facility for research and training. Combined with CDC and other resources you have the basis for a large federal research effort that entirely avoids commercial use.

    I propose that the federal government take over antibiotic and vaccine research, license all discoveries, and establish themselves, by default, as the sole manufacturer, and arbiter of who may purchase and how their product is used. Doctors would have to apply on a case-by-case basis to use an antibiotic. Conditions of sales and use would vary between a dose-by-dose accounting, similar to schedule I drugs on the low end, to demands that any use occur only in federal high security bio-control facilities where even sewage is incinerated to limit exposure of bacteria to the antibiotics.

    Specialized antibiotics would be escorted, by armed federal agents if necessary, from point of manufacture to end use.

    This would not preclude private enterprise development of antibiotics and vaccines. If any drug company wished to undertake the research necessary to sell their product they would be free to do so. Use would remain regulated to prevent grossly inappropriate use.

    The odds are that essentially all research would be federal and the private pipeline would consist of existing antibiotics and, in time, third-string antibiotics released for commercial use.

    Yes, this is extreme, but neither doctors nor pharmaceutical companies have shown any ability to limit and husband the use of these precious resources and commercial interests have been lagging badly in their level of investments in research on new antibiotics and vaccines. Commercial pharmaceutical manufacturers are not structured to effectively allocate a limited resource to maximize benefit for humanity. They are optimized to maximize profits. It is time to stop messing around with half measures and get serious.

  35. mnb0 says

    “you’ll be frightened”
    Personally yes – but I’m frightened of all kind of diseases; an example is kidney stones. But generally speaking I think Earth would be better of if the human population decreased to 10%. Now I have a serious ethical problem with humans killing off 90% of fellow humans. So if I can contract out the job to superbacteria who will not show remorse and are our enemies anyway no, that doesn’t frighten me.
    It will be a tough time for Homo Sapiens and being an egoist I hope my loved ones won’t suffer.

    “The threat of the end of antibiotics”
    Note that most proposals only postpone the bacterial apocalypse.

  36. terminus says

    It may be that the only reliable way to fight bacterial infections is to re-establish normal flora populations. This has proven effective in the battle against C.diff and other intestinal infections, using treatments like fecal implants, drinking “yellow soup” – yep, that’s exactly what you think it is – and the development of bacteria-containing capsules that can be swallowed.

    I recently discussed these possibilities with my AP Bio students and they agreed that induced competition is one way to avoid the inevitability of antibiotic resistance.

    FYI, any expert commentary will be relayed to my classes.

  37. seranvali says

    I picked up two of those damned things while I was in hospital having cancer treatment. Fortunately for me, while antibiotics made no difference at all, probiotic yoghurt got rid of it in about a week.

  38. ryanb says

    @Bret #31

    “What makes you think it would be cheaper to do that?”

    Cheaper? Pharmaceutical companies aren’t doing it anyway! For reasons that there isn’t any profit or there’s too much risk (in the case of phage therapy a big hang up in terms of monetization is that there are so many potential different phages for the same bacteria that patenting becomes untenable). If a socialised system was developed to focus on medical development that would be beneficial to society but with no profit then we could have medicines that the market isn’t providing for us.

    “On top of that, which drug research priorities you pursue are now much more heavily politicized as opposed to the prior system, where drugs get research money as long as the company thinks they stand a chance of making a profit on the discovered drug. Who decides which drugs get money for research and clinical trials?”

    It’s not that hard to conceive of a regulatory body made up of industry and academic experts that determine this. There are many examples of good biomedical bodies that already do this, hell a significant portion of academic funding comes from charities, they’re not looking for profit but somehow they manage to come up with protocols for how to determine what would be best to fund.

    Furthermore your argument seems to be that the current system is working. Evidently it isn’t else we wouldn’t be having this discussion.

    “We know what a fully socialized health research set-up looks like, from the Soviet Bloc countries. It was not a source of great medical innovation, unless you want to count biological warfare.”

    Socialised research already happens in the west; ever heard of government funding or government labs? My proposal was to take it further with regards to pharmaceuticals. And as for the soviets, you realise this thread started with a post on phage therapy? A field with huge potential that almost exclusively was developed by soviets?

  39. franko says

    A lot of these comments seem to assume that discovery of antimicrobial agents is simple science and that big pharma doesn’t bother because the drugs aren’t profitable enough. The reality is that many big drug companies have made perfectly good profits from antibiotics (life-saving drugs can command high prices). They’ve given up on finding new ones because new types of antibiotic just haven’t emerged over many years from research in industry or academia.

    From the 1980s the nature of antibiotic discovery research shifted from blind screening of natural products and synthetic chemicals for serendipitous discovery of antibiotics (essentially the approach used for many years after Fleming discovered penicillin) to “rational design” of molecules active against defined target molecules in bacteria. News media were filled with reports of scientists who’d found a new target for antibiotics; it could only be a matter of time…

    In the 1990s along came the possibility for whole-genome sequencing of bacterial pathogens. This led to the belief that a bacterial genome would lead to antimicrobial discoveries. Surely, the massive power of molecular genetics would fill the enlarging hole for new antibiotics?

    Sadly, this stuff never worked out. Read, for example, Payne et al., Nature Reviews Drug Discovery 2007, vol. 6 pp. 29-40. (Sadly, this is a pay-per-view journal if you don’t have access in your library.) This article, by the head of antibiotic discovery at Glaxo-SmithKline (GSK), sets out in detail how the rational, target-based approach didn’t bear fruit. The experience of GSK was reflected in all the other companies trying to discover new antibiotics. And there is only so much time and money that can continue to be invested in any discovery project.

    Nowadays there are still a few large companies — and plenty of academic research groups and biotech entrepreneur companies — endeavoring to discover new antimicrobial agents. The task is far from easy but the need is undoubtedly great. The problem is the remarkably low success rate of this type of research.

  40. ledasmom says

    I would be dead without effective antibiotics (note: It is not good to put yourself in the position of being the bad example the ER doctor points out to another patient to show him what his arm should not look like). It is sort of starting to anger me that we (meaning specifically the U.S., which I have the most knowledge of) have known this was a problem for a while, and we have known some of the things we could do about it for a while, and nevertheless we have not done them.

  41. ryanb says

    @Franko #43

    Whilst antibiotic research has become more difficult over time (unsurprising given the phenomenon of low-hanging-fruit in research) the real discussion is phage therapy. Whilst it’s still unclear how positive an impact phage therapy could have in the treatment of infectious disease it’s well accepted that the two major hurdles to further research are regulatory hurdles and lack of market interest due to the high unlikelihood of patents. If the regulation for the research and testing could be sorted (and as major changes have already been made in recent years like the Advanced Tissue Therapies regulation it wouldn’t be impossible) then the only real option after that is public funding. There’s no market interest in an expensive venture that has limited-no ability to be patented but there is a huge public interest.

    This review goes into more detail on this topic for those interested:
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821673/

  42. franko says

    @ryanb #45

    Phage therapy is a great idea. But its problems have been outlined by other commentators, and in the review you cite. All we need is a broad-spectrum phage that (ideally) can be administered orally and IV without inducing any host immune response and we’ve broken the back of the problem. Of course, bacteria may develop resistance to a widely used therapeutic phage (they evolved restriction endonucleases and collect bits of phage genomes in the effort to resist them) but that’s a problem for later on…

  43. raven says

    They’ve given up on finding new ones because new types of antibiotic just haven’t emerged over many years from research in industry or academia.

    This is correct and explained well. I’ll just add some examples.

    1. One old, and large soil screening program finally gave up. They didn’t discover a new antibiotic in the last few decades. They find the old ones over and over.

    The environment has been marched through for close to a century worldwide looking for magic bacteria i.e. antibiotic producers. It looks like they’ve discovered more or less all of them using current technology.

    2. One group screened/made inhibitors of intracellular housekeeping genes, biosynthetic inhibitors. In vitro, they worked great. They didn’t kill bacteria. It turns out, bacteria live in a tough world and they are very picky about what they let into their insides. Transport problems.

    What mostly reduced new antibiotic development was the simple fact that people couldn’t discover any more. Huge expensive programs just failed. No one is quite sure why but the “Low Hanging Fruit” theory covers it. It might be that almost all the best ones have been found.

  44. franko says

    @raven #47

    You’ve raised another facet of the problem. Allow me to philosophize about biodiversity. On the one hand we are pleased to discover that all living organisms on the planet work in the same way: DNA encodes RNA, which encodes proteins. Occasional exceptions (minor genetic code translation differences, RNA viruses, etc.) don’t mar the principle. All current life forms have evolved from predecessors which work in the same way.

    On the other hand, we somehow expect biodiversity to throw up an infinite number of new molecules. Is infinite molecular diversity realistically possible given that everything living works on a common molecular-genetic mechanism?

    In the past I’ve been involved with screening for antibiotics from types of organisms that had never been previously explored. Every time we found inhibitory activity the molecule concerned was either one we already know or a variant with an extra methyl group here or an amine there. No new classes of antibiotics at all!

  45. raven says

    In the past I’ve been involved with screening for antibiotics from types of organisms that had never been previously explored. Every time we found inhibitory activity the molecule concerned was either one we already know or a variant with an extra methyl group here or an amine there. No new classes of antibiotics at all!

    Yeah I know.

    Drugs from the sea has been a big push for the last few decades. They’ve found some interesting compounds but I can’t think of any offhand that made it to the pharmacy shelves.

    There are a lot of new approaches to try to develop new antibiotics. They are going to be cutting edge technology, expensive, and there is no guarantee they will work either.

  46. says

    I think it is naive in the extreme to assume that patent extensions and easier drug trial requirements will effectively address this issue. These incentives still leave priority-setting and management of what is shaping up to be major public health crisis in the hands of private companies who will prioritize based on profit–not on actual need. This is their role. They are vilified for it, but the real problem isn’t that pharma puts shareholder profits over people (of course they do–they aren’t charity orgs), it’s that we keep allowing them to control public health priorities knowing full well they are not capable of doing this.

    We have already seen what patent extension and loosened trial requirements wrought for drug development in the rare disease arena where these types of incentives have been used since the mid-80s. Pharma has taken advantage of the incentives and drugs for rare disorders have been developed, but with only the carrot (incentives) and no stick (no regulatory input on priorities or pricing) the prices on some of these drugs are exorbitant. There are several such drugs on the market already (Kalydeco for CF with a price tag of $300,000 per year FOR LIFE; Rivicti for UCDC with a price tag in the $400,000 per year FOR LIFE range) and analysts are predicting we will see our first $1,000,000 a year drug by 2015.

    We’ve also already seen what happens with antibiotics when pharma recognizes a profit opportunity. Cheap off-patent antibiotics (like tobramycin and aztreonam) have been reformulated for different delivery systems (e.g. tobramycin now available as ‘TOBI’ and astreoman as Cayston for inhalation) and re-patented as new drugs. In this way, drugs that cost $10 – $100 a month are now fetching $5,000-$6,000 a month.

    If the plan is to incentivize pharma to fix this problem, we are doomed. Direction, priorities and resources need to be set by public health officials.

  47. opposablethumbs says

    Direction, priorities and resources need to be set by public health officials.

    This. QFT.

  48. unclefrogy says

    some where in the last few weeks I heard a story on NPR about a study on livestock and antibiotics that showed that there was no great weight gain differential in the animals fed prophylactic antibiotics compared to other ways of using them. the story might have been in conjunction with new regulation but I took it as a positive development.
    It might be that the belief that antibiotics fed to livestock for weight gain was based on poor studies and marketing then good practical studies. Rather like the way other chemicals are sold to agriculture like the over use of herbicides and insecticides. The way to “sell” better practices to agriculture is to demonstrate that a more integrated approach and targeted use of chemistry is cheaper in the end.
    I would suggest that a similar approach would mitigate the inherent problems of antibiotics and pathogens. All the market forces involved in medicine are lined up against cheaper and wiser because we are lazy and want the easy quick answer magic over ordinary hard work . We do not want to be “Dr House” in practice and really want to know what is going on we just want the job so we can make a good living. That is how healthcare looks by the results were are getting .

    uncle frogy

  49. says

    Sadly, this stuff never worked out. Read, for example, Payne et al., Nature Reviews Drug Discovery 2007, vol. 6 pp. 29-40. (Sadly, this is a pay-per-view journal if you don’t have access in your library.) This article, by the head of antibiotic discovery at Glaxo-SmithKline (GSK), sets out in detail how the rational, target-based approach didn’t bear fruit. The experience of GSK was reflected in all the other companies trying to discover new antibiotics. And there is only so much time and money that can continue to be invested in any discovery project.

    Snort.. Well, yes and no. In reality, it turned out to be, well.. way more complicated. You have multiple problems –

    1. Does it only target your target, or other things too?
    2. Is what you are targeting the right target?
    3. Does it have other effects, someplace else, which will make it useless.
    and, well… 4. Sometimes the system you are targeting is complex enough to make it damned hard to figure out any of 1-3 above.

    Progress “is” happening, but, often on less complex things, like specific targeting cancers, or designing drugs to target the GABA chain, and the like. With antibiotics.. you have two major issues. The first one is that you are dealing with something that is, ironically, more complicated than the stuff that these things are working for, and second, its a bloody moving target, so, even if the “version” of a microbe in the lab “is” effected by it, there is no certainty that the “wild” versions will be.

  50. Fred Bacon says

    Last year I bought a puppy. When he was about three months old, I took him out for a walk one Friday night. He picked up a peice of “road kill” by the side of the street which he refused to drop. I had to take it away from him. In doing so, I just barely scratched my finger on one of his sharp little puppy teeth. It oozed a couple of drops of blood. I finished my walk and went home. I washed off the scratch and put a bandage on it.

    Saturday: All was well.

    Sunday morning: I awoke to realize that the wound was a little tender. An hour later, there was some swelling and fluid under the skin. It started to get really red and tender. I went to the emergency room and got some antibiotics. By Sunday afternoon, I had a fever and my finger was the size of a bratwurst.

    It wasn’t that long ago that my grandfather died of pneumonia because antibiotics were still rare. Perhaps we’ve been lucky to live in a golden age.