Ringer Posted October 16, 2013 Posted October 16, 2013 Ok, so what are they? I could suggest designing a oncolytic retrovirus (http://en.wikipedia.org/wiki/Oncolytic_virus) - specifically VSV (http://en.wikipedia.org/wiki/Vesicular_stomatitis_virus) with a transposon (http://en.wikipedia.org/wiki/Transposable_element) that cause apoptosis of cancer cells (http://en.wikipedia.org/wiki/Apoptosis) - specifically LINE-1 (http://link.springer.com/article/10.1186%2F1475-2867-6-13). Oh wow I just invented a cancer vaccine! Guess we'll have to race to that Nobel prize nomination. However, without specifics, such a suggestion is simply a fanciful speculation, and fanciful speculations are worth little. This made me laugh because I had a similar thought and was answered with "I haven't mentioned using viruses so I don't know where you got that from?".
John Cuthber Posted October 16, 2013 Posted October 16, 2013 The organisms under consideration for use as a bio-agent are known as obligate anaerobes. Wikipedia: Obligate anaerobe Just like C perfringens which causes gas gangrene. http://microbewiki.kenyon.edu/index.php/C._perfringens You really ought to stop assuming that your ideas are right. So, now that we have disposed of that idea (hopefully, once and for all). We can have another look at the other ideas you have put forward. "The sort of bio-agents and drugs I need for my approach are real enough." Then they are already the cure for cancer and your whole thread is redundant. And you seem to have missed this point: If your magic regimen of intensive care saves the patient- it will save the cancer too.
Peter Dow Posted October 17, 2013 Author Posted October 17, 2013 (edited) I take it that you have not responded to my post earlier because you realise I'm right.. I think you'll find that I have responded to all previous posts which are making scientific points. Patience please. I am now responding to post #30 and the newest posts are numbering around #53. You may feel ignored but it is simply that there is a queue to be processed. So I am a long, long way behind with the backlog of posts to reply to and you'll just have to wait until I have time to post my replies which will usually be in the same order to the order which the posts I am replying to were posted. in any event this Do you expect the patient to be completely cured in a week? Only for those patients whose cancers have cells which are rapidly dividing, whose cancer cells divide every few days. For those more aggressive cancers the cure is more rapid. For slower growing cancers you have to keep the treatment going for longer, perhaps have treatment on, treatment off weeks, waiting for the opportunity to catch and kill each cancer cell as it divides. would be funny, if it weren't tragic. You can't (repeatedly or continuously) suspend human cells growth for weeks and expect the patient to live. So you are really asking about how practical treatments lasting for weeks, on and off, are? It is just that you quoted Ringer asking about curing treatments in only a week but your question didn't ask about that, but about longer treatments. So you haven't made it clear whether you expect me to explain further about that point. Anyway, briefly on the first point, more aggressive treatments are easier to cure because the cells are always dividing and so you don't have to wait long to kill all the cancer cells. It is the slower-growing cancers who cells pick and choose their time to divide that require a more extended treatment regime. Anyway back to your question John, it is not meant to be funny and my approach is aimed at reducing the tragedy of so many cancer deaths. Well if a full recovery can be made in a few days, building up the patient's strength, especially as regards those rapidly dividing cells, then the expectation is that the patient would be more healthy, not less healthy, at the beginning of each week on, compared to the beginning of the previous week on. What you seem to be forgetting is that if the patient stops taking the drugs then the suspension will stop, the cells will resume normal division. This is a treatment wherein because it is only cancer cells that are being killed so then the recovery is very rapid, unlike say with bone marrow transplants now when a lot of normal cells which were dividing when the chemotherapy was done, were also killed at the same time. That chemo takes a lot out of the patient and recovery is slow. My approach spares the patient that long recovery time. Incidentally, you won't get far trying to pretend that using a sequence of treatments for cancer is a new idea. http://en.wikipedia.org/wiki/Chemotherapy_regimens Your link only supports the notion of multiple drugs regimens, not phased treatment plans. If you can come up with a link which shows a phased approach, bio-agent / bacteria in phase 1 followed by chemotherapy in phase 2 then I will concede your point but only if you find such a link. I don't know of one. This is my approach described here. Not someone else's. This could be new, I don't know of anything the same but you never can be sure. You could use your analogy if you had any idea how phase 2 would work, but you don't. You have an overview of how you think something might work (that would kill your patient). So literally the only thing you brought was an already existing treatment and talk of hypothetical wonderdrug. It works like this and in the following sentence "H" stands for the use of the type H drugs to stop normal cell division but leave cancer cells still dividing and "K" stands for the use of type K drugs to kill all dividing cells Ready? OK If H works then K kills only cancer cells. If H doesn't work then K kills both types of cells So if you understand that short summary then you ought to understand that my approach works if type H drugs work as advertised. Got it yet? Really? You won't even try to talk about it in context? Questions can be hard enough to answer without having to guess at the context the poster was thinking about but was too lazy to actually type in. FFS man, the point is that the bacteria will be uncontrolled because this wonderous hypoxic environment is the entirety of the human body. No, that's almost entirely wrong. The entirety of the living human cells in the human body experience a suitable oxygenated environment to allow them to use aerobic respiration. Now sure, you could have parts of the body with no human living cells there and at those places alone there the oxygen levels could be hypoxic, maybe. Certainly, if the human is not happily breathing air, if the body is injured and the blood flow is obstructed, not getting oxygen to some cells - sure then hypoxia is certain. Look Ringer, aside inside from our digestive tract and inside the bladder where the urine is, where can you find a single cubic inch of the healthy human body which is all hypoxic and what is there at that place for anaerobic bugs to eat? I don't think you can name such a cubic inch but make my day. If that were true, how would you expect to cure a cancer of the digestive tract? Cancers must be of the living digestive tract cells which have blood vessels supplying them oxygen same as most other cells do. It is only the inside of the digestive tract - which many anatomists would describe officially as "outside the body" (kind of strange way to look at things I know) - it is only inside the digestive system and inside the bladder too where there is much of anything which is hypoxic. So you're just making stuff up? People here have already tried to help fill in the details that your idea doesn't work very well, and you just repeat that everyone else is wrong. Well what I am finding is that chemists don't know their biology and biologists don't know their chemistry and the doctors are in the middle of this watching the scientists battle it out and trying to be helpful! Yeah, but that transplant has a higher reward than risk factor. Your treatment will kill way before a cancer does, so the analogy is moot. Well I would say curing cancer is the reward and my treatment has fewer dangers. 1.) What does the diversity of species in gut bacteria have to do with the fact that your bio-agent kills anything in a hypoxic environment and the gut is a hypoxic environment? Well the bio-agent won't be killing anything inside the gut, nor is it supposed to. That's not where the cancer is. 2.) People won't have an active immune system because halting cell division has ended in new anti-bodies being produced so your bio-agent will overrun the body Ah you are mixing up your phases. The bio-agent is only needed for phase 1. After phase 1, the bio-agent is killed off using a large dose of anti-bio-agent drug. Before phase 2, the gut flora need to be killed off as well. So yes the immune system is an issue but a manageable issue. And it would still by meaningless to the question I have asked. Sorry what was the question again? Edited October 17, 2013 by Peter Dow -1
Arete Posted October 17, 2013 Posted October 17, 2013 No, that's almost entirely wrong. The entirety of the living human cells in the human body experience a suitable oxygenated environment to allow them to use aerobic respiration. Are you sure you don't have difficulty with reading comprehension? It's been pointed out to you repeatedly by multiple posters that the above statement is untrue: you are confusing anaerobic/aerobic cellular respiration with aerobic/anaerobic environments. They are not the same thing, and have lead to the above fatal flaw in your entire proposal. Most of the human body is an anaerobic environment. The reason large tumors are referred to as anaerobic is not because there is no air there, it because there is limited blood supply – leading the cells switching to glycolic respiration. You still appear to be conflating respiration with environment. So, muscle tissue is anaerobic enough for anaerobes to grow and at least some cancers- enough that they got their collective name from it- are well supplied with blood and, therefore, oxygen. You still seem to be having trouble with the fact that glycolysis (i.e. anaerobic respiration) is not equitable with a hypoxic environment. No one is debating that most cellular respiration is aerobic. However, for that respiration to take place, cells a need constant supply of oxygen delivered to them via the circulatory system. Without the circulatory system, aerobic respiration rapidly ceases. This is because the ambient oxygen level is too low for aerobic respiration to occur. This in turn means that the interior of your body is, you guessed it - anaerobic. That should also be evident to anyone who’s studied basic biology. By the measure that I specifically mentioned earlier. You know, that the circulatory system is necessary because the body is hypoxic.
Peter Dow Posted October 17, 2013 Author Posted October 17, 2013 (edited) So it's no longer a cure for cancer but a treatment for a specific type? Well I have been consistent from my OP that not all types of cancer will respond to phase 2 treatment. I'm not chopping and changing my story. The issue is whether the cancer cells divide more in response to typical growth factor signalling. Let me give an example or two. Example 1 - cancer can be treated by phase 2. Before treatment with type H drugs Normal cells of tissue type X divide once every 4 days and the number of them stays the same because new normal cells replace the normal cells which have died Cancer cells of tissue type X divide once every 2 days and the number of them grows because there are more new cancer cells than any cancer cells which might have died So in that case the same body cell signals make the cancer cells divide at a faster rate than normal cells, every 4 days for normal cells, every 2 days for cancer cells. That's a cancer simply because the cancer cells are dividing at a quicker rate but not dying at a quicker rate During treatment with type H drugs Normal cells of tissue type X have stopped dividing thanks to type H drug Cancer cells of tissue type X still divide once every 2 to 3 days despite type H drug which only has a small effect to slow their division but the cancer cells are killed by the type K drug when they divide so, so after 3 days all the cancer cells are dead but the treatment lasts for 4 days just to be sure to kill all the cancer cells Example 2 - cancer cannot be treated by phase 2. Before treatment with type H drugs Normal cells of tissue type X divide once every 4 days and the number of them stays the same because new normal cells replace the normal cells which have died Cancer cells of tissue type X divide once every 4 days and the number of them grows because none of the cancer cells are dying So in that case the same body cell signals make the cancer cells divide at the same rates as the normal cells, every 4 days. That's a cancer because those cancer cells are all immortal, they don't die like they should, ever. During treatment with type H drugs Normal cells of tissue type X have stopped dividing thanks to type H drug Cancer cells of tissue type X have stopped dividing thanks to type H drug Type K drugs don't kill any of the cells. Also, wouldn't it be easier to force apoptosis? since your drug is hypothetical you should probably go for the most effective thing. No. We have the kind of drug which can block growth factor receptors in some tissue types already. Wikipedia: Growth factor receptor inhibitor So the type of drug is not "hypothetical". We just need more of that type of drug for other tissue types, other growth factor receptors. That's something well within the abilities of big pharma to deliver eventually. That science is known about. So my approach whilst not "easy" can be realistically planned for. We don't have any kind of drug which can force apoptosis in every cancer cell but leave all normal cells alone, I think. That science is unknown I think and I am fairly sure no such drug is currently being sold for treatment. It is not realistic to plan any approach like that before anyone has demonstrated a drug which forces apoptosis and treated some patients with it successfully. If such a very useful drug could ever be demonstrated then yes then it would be possible to plan an approach for that but I don't think it has been demonstrated. So my approach would be a lot easier. So you have no idea how your treatment would work? Scientists, engineers, and physicians already have plenty of overviews of viable ways they can treat cancers. What they don't need is someone trying to reinvent the wheel and expecting them to do all the work to see if it is even a viable possibility without so much a doing research on the ongoing progress of the field. I know exactly how my approach would work with the types of cancer where it would work well and some ideas of what to offer where it doesn't work so well - maybe just in phase 1 will it do much. So it is not a cure all. I never said it was. I said it wasn't. Edited October 17, 2013 by Peter Dow -1
Endy0816 Posted October 17, 2013 Posted October 17, 2013 Main issue is that this isn't a Scientific Journal or even one of the less than Scientific Journals out there. The next Einstein could publish here and would have a rough time of claiming credit, let alone a Nobel prize. Most of what you write is also vague. You don't get points in science for vagueness. The guy who says: "Hypocortisine in a 5 mg dose along with a 30 mg dose of Thetrazine, will cure Trewq Cancer in 9-10 days." will get the credit. Besides that as has been mentioned your "cure" would kill the person and then some. There are real world novel treatments out there that are safer by far. That's what is going to get the research.
CharonY Posted October 17, 2013 Posted October 17, 2013 (edited) If this was a scientific journal we would not have this discussion at all. Edited October 17, 2013 by CharonY
John Cuthber Posted October 17, 2013 Posted October 17, 2013 If this was a scientific journal the OP wouldn't have got passed being laughed at by the editor, and possibly a few reviewers who the editor felt like cheering up. (at least, that's my opinion, but a friend of mine is an editor of a bioscience journal if you would like me to check the validity of the statement). 1
CharonY Posted October 17, 2013 Posted October 17, 2013 Eh, one would not send that to reviewers, it would reflect poorly.
Arete Posted October 17, 2013 Posted October 17, 2013 Eh, one would not send that to reviewers, it would reflect poorly. The tell for me is the fact that he's only ever cited wikipedia. Furthermore, if you follow from post #38 to #46 to #48, it looks like he's creating the wikipedia pages he's subsequently using as citations. It's like a textbook example of why wikipedia alone is an insufficient source of citation, and why an armchair, wikipedia education isn't going to win you a Nobel prize.
CharonY Posted October 17, 2013 Posted October 17, 2013 Indeed. Or anything else but a passing grade in one of the entry-level courses. What is weird to me is that some people string together some facts and factoid and believe they actually have discovered something. Reminds me of kindergarten or elementary school days when kids mix two colors and are fascinated by the "invention" of a new one (that conveniently already has a name). Well, the latter is kind of cute, though.
John Cuthber Posted October 17, 2013 Posted October 17, 2013 The tell for me is the fact that he's only ever cited wikipedia. Furthermore, if you follow from post #38 to #46 to #48, it looks like he's creating the wikipedia pages he's subsequently using as citations. It's like a textbook example of why wikipedia alone is an insufficient source of citation, and why an armchair, wikipedia education isn't going to win you a Nobel prize. To be fair, most of what I cited was also wiki. The difference is I understood it. 1
Ringer Posted October 18, 2013 Posted October 18, 2013 (edited) It works like this and in the following sentence "H" stands for the use of the type H drugs to stop normal cell division but leave cancer cells still dividing and "K" stands for the use of type K drugs to kill all dividing cells Ready? OK If H works then K kills only cancer cells. If H doesn't work then K kills both types of cells So if you understand that short summary then you ought to understand that my approach works if type H drugs work as advertised. Got it yet? Oh my god, I think I get it. I understand now that you have repeated the same generic overview of a hypothetical process with no mention of the actual mechanisms. It means something now that it didn't the past 20 times. Questions can be hard enough to answer without having to guess at the context the poster was thinking about but was too lazy to actually type in. Then don't snip the context out of the quote. [edit] after looking back I see that the context was there and you just ignored it. To make it simple: Circulatory system = Problem with your idea that the body is oxygen rich Circulatory system =/= and evolutionary problem [/edit] No, that's almost entirely wrong. The entirety of the living human cells in the human body experience a suitable oxygenated environment to allow them to use aerobic respiration. Then please do tell why we have a circulatory system, it seems unnecessary with all the molecular oxygen flying about. Now sure, you could have parts of the body with no human living cells there and at those places alone there the oxygen levels could be hypoxic, maybe. Yeah, like the spinal chord right? Certainly, if the human is not happily breathing air, if the body is injured and the blood flow is obstructed, not getting oxygen to some cells - sure then hypoxia is certain. That's the damn point. Breathing is necessary because the body is a closed hypoxic environment so we need specialized systems to bring oxygen to cells. Look Ringer, aside inside from our digestive tract and inside the bladder where the urine is, where can you find a single cubic inch of the healthy human body which is all hypoxic and what is there at that place for anaerobic bugs to eat? I don't think you can name such a cubic inch but make my day. Somewhere the body is hypoxic? Crap, you got me. . . Wait, how about anywhere there is not continuous blood flow, outside cellular membranes, connective tissues, most areas of epithelium, anywhere encased in cerebrospinal fluid, anywhere you feel sore, etc. etc. etc. Cancers must be of the living digestive tract cells which have blood vessels supplying them oxygen same as most other cells do. It is only the inside of the digestive tract - which many anatomists would describe officially as "outside the body" (kind of strange way to look at things I know) - it is only inside the digestive system and inside the bladder too where there is much of anything which is hypoxic. Incorrect, I'm starting to think you may not know the difference between hypoxia the medical condition and a hypoxic environment. Or you're trolling, or you don't really care to think that people with experience in the field of biology have any idea what happens in biological systems. Well what I am finding is that chemists don't know their biology and biologists don't know their chemistry and the doctors are in the middle of this watching the scientists battle it out and trying to be helpful! If you gave any real biology or chemistry you might have a point. Or maybe this joke is a vague overview of something that you had an idea to talk about but can't really get the point across in words? Well I would say curing cancer is the reward and my treatment has fewer dangers. Except the whole killing the patient Well the bio-agent won't be killing anything inside the gut, nor is it supposed to. That's not where the cancer is. Truly?!?!?! You know where all the cancer is?!?!?!??! Ah you are mixing up your phases. The bio-agent is only needed for phase 1. After phase 1, the bio-agent is killed off using a large dose of anti-bio-agent drug. Before phase 2, the gut flora need to be killed off as well. So yes the immune system is an issue but a manageable issue. Really? How will the immune system damage be managed? Please tell me this thoroughly detailed regiment has a great way to do this. Sorry what was the question again? Did you know that you can look at what was typed in the past? This is a new question but if answered correctly it should lead you to the original question. Edited October 18, 2013 by Ringer
Greg H. Posted October 18, 2013 Posted October 18, 2013 I am having a very hard time maintaining my composure and not trolling this thread so hard, the forum server quakes in fear. Will someone please put this thread where it belongs?
Peter Dow Posted October 18, 2013 Author Posted October 18, 2013 (edited) Peter, Do you know where the name "Cancer" came from? It comes from the Greek for crab. The tumour was often noted to have blood vessels that resembles the many legs of a crab. Yes I knew that already but thanks for the etymology lesson anyway. So, at best these cancers might be marginally anaerobic. Well cancers vary a lot and some do grow faster than the body can sprout vessels to supply the tumour and those are the only tumours which have hypoxic cores, other tumours don't, correct. Phase 1 treatment is only intended to treat hypoxic tumour cores, cores that are properly hypoxic and where cancer cell division has ceased because there's not enough oxygen to divide. Right from the OP, phase 1 was never intended to treat "marginally anaerobic", slightly hypoxic tumour cores or tumour cores with good blood vessel supply. Right from the OP, the limitations of phase 1 were made clear that it was never intended to treat the rim or periphery of any tumour or the whole of smaller tumours which will be well oxygenated because they are so small that oxygen can get into the middle of them, even if they haven't grown their own blood vessels. If I had thought for one moment that phase 1 was a complete cure, I would not have bothered with a phase 2. Phase 1 is guaranteed to achieve phase 1 goals as advertised, no more, no less. Onthe other hand, you may remember that I posted a reference to gas gangrene. It destroys legs and arms etc and is caused by this bug http://en.wikipedia.org/wiki/Clostridium_perfringens which is an anaerobic organism. So, muscle tissue is anaerobic enough for anaerobes to grow and at least some cancers- enough that they got their collective name from it- are well supplied with blood and, therefore, oxygen. Do you see how that's a problem? Woah there; steady on! From that Clostridium perfringens Wikipedia article you linked to This is a problem in major trauma and in military contexts. That's when gangrene is a problem because a major trauma, like having parts of your body pinned under something heavy for hours or getting shot in war, causes a massive quantity of your body tissue to lose its supply of oxygen and that is indeed a problem for the oxygen-deprived tissue - it is called ischemia - Wikipedia: Ischemia which becomes an opportunity for anaerobic bacteria. Without immediate intervention, ischemia may progress quickly to tissue necrosis and gangrene within a few hours So muscle needs to be ischemic for an anaerobic infection to take hold in that muscle in the first place. No ischemia, no gangrene. It's not the case that if you inject a strictly anaerobic bacteria into healthy tissue that the anaerobes can cause an infection at that location. No; healthy tissue is too well oxygenated for anaerobes to proliferate. So they'd just be dormant, just stuck in place doing nothing or circulating around until dealt with by the immune system. It's different in ischemic tissue and it is different in hypoxic tumour cores. Gangrene needs ischemic tissue to get started. It can only spread from where it has established a large "base of operations" so to speak, where large quantities of tissue are hypoxic, ischemic, necrotic because some injury or disease state has blocked off the blood supply to those parts of the body. In order to spread into healthy tissue the anaerobe needs to kill the healthy tissue from outside it and the only obligate anaerobes which can do that have very lethal toxins which large bacterial infections can make enough of so that when the toxin seeps into the neighbouring healthy tissue there's enough toxin to kill the healthy tissue and so the infection can spread. Now for use as a bio-agent in phase 1 you'd pick an anaerobe that didn't have a very lethal toxin, maybe make a genetically-modified anaerobe, like Clostridium novyi-NT, which didn't have that ability to kill healthy tissue from outside that healthy tissue. Then you'd also have the anti-bio-agent drug to moderate the infection, reduce the activity of the bio-agent so that any toxins it was making were being made in such small quantities that they were easy for the body to dispose of safely. And the answer to "Then I wonder how your fellow anatomy 101 students will react to your claim that "Most of the human body is an anaerobic environment."? " is probably, just fine because most of it is, at best, marginally aerobic. Well the fact is most of the body consists of living body cells and where they are, they have oxygen thanks to the blood and these critical areas are not somewhere the obligate anaerobes can proliferate. If an obligate anaerobe can find some nook and cranny of the body which is hypoxic enough to activate and is lucky enough to find enough resources located at that nook and cranny to become active in tiny numbers that's no big deal because an obligate anaerobe still has the problem of finding a further food source to proliferate. There isn't that much of the body normally, that doesn't have oxygen enough to deactivate obligate anaerobes. So they'd be stuck active in that nook and cranny and maybe sending a few spores out now and then but not proliferating significantly because they can't. They are surrounded by oxygenated tissue and that pens them in. If a good selection of bio-agent is made gas gangrene would not be the problem you claim. If with some patients who already have ischemic and nectrotic tissue because of some other disease, or perhaps the cancer tumours have blocked blood vessels to other parts of the body then yes, of course, then there is more of a risk of gangrene in those cases but that threat is more likely from other anaerobes, the ones like Clostridium perfringens most commonly associated with gangrene, not from the bio-agent which is selected so that is doesn't find it easy to spread to healthy tissue. So some cancer patients do get Clostridium infections and gangrene and some die from it but that's usually down to inadequate medical care. By the measure that I specifically mentioned earlier. You know, that the circulatory system is necessary because the body is hypoxic. I'd prefer to phrase it this way - the body cells are not hypoxic thanks to the functioning of the circulatory system. So most of the human body ... and all of the cells of the body are well saturated with oxygen and not hypoxic, not in the least low in oxygen. You have implied, and stated in passing, that it will be bacteria. Either way, what will keep the bio-agent from becoming resistant? Ah at last - a different question. How refreshing! The development of drug-resistant strains of bacteria depends on those strains being able to keep themselves going by spreading from patient to patient. The bio-agent reference samples will be stored in an isolated laboratory and will not be mutating in vitro in the lab and if any samples ever did, they'd be disposed of. The bio-agents to be used will be bred from the reference samples. They won't have time to mutate in-vivo before they are killed off before phase 2. In any case, if a patient jumps out of his bed after phase 1 goes home and in 20 years the bio-agent in his body has mutated to a drug resistant strain it matters not because we won't be breeding bio-agent from the bacteria in that ex-patient but from the reference samples in the laboratory. Your concern is as logical if you buy a pure bred puppy from a dog breeder but you are worried that other dogs might have escaped from the dog breeders kennels and have bred with other stray dogs to produce mongrels, not pure-breds. Well, so what, so long the puppy you get is a pure-bred you should be happy so quit your whining. Then you should probably actually explain things better. If a group of people that have experience in the field of biology are all having similar 'misinterpretations' of what you mean it's probably a problem with the message. I should explain things better. Millions of lives are depending on that. Sadly you have eliminated any immune reaction to the bio-agent so you don't have to worry about that. Still mixing up your phases I see. No, the immune system is not eliminated; it is not even weakened in phase 1. It's there full strength to help to contain the bio-agent. Again, when the misunderstandings are consistent you should probably rework how you are writing. Well I am re-working and adding useful examples as I go along. The first OPs I posted in science forums were somewhat rushed and inadequately presented because I was eager to share my "Eureka" moment with you all and hadn't taken the time to research the answers to some important questions I had, like a few type H drugs are indeed available now used as "growth factor receptor inhibitors". you didn't say this "Oh my approach doesn't require "modifying" bacteria. My OP didn't mention "modification" of bacteria to do anything other than what comes natural to bacteria"? I did say that but that was in response to someone claiming I was looking for, can't remember the exact words, something like "magic" bacteria, whereas, no, it is simply selecting the best for the bio-agent job which are available from obligate anaerobes, whether native or genetically-modified strains. The point I was making was that what is required for the bio-agent is not some mythical beast but the most suitable out of what is there and so by all means pick an existing genetically-modified strain like Clostridium novyi-NT if tests prove that to be the most suitable when compared with the 100s of native obligate anaerobes out there. I was just making the point that the behaviour required from the bio-agent desired is characteristically typical behavior, not at all science fiction. I am now including a link to Wikipedia articles about Clostridium novyi-NT in the latest versions of my OP posted elsewhere because that often comes up in discussions, but my approach is in no way founded upon that GM strain, as if the approach would fail without that strain. You should probably not grossly misunderstand a simple point when you are accusing everyone else of not being able to understand this area. I don't misunderstand. They should be fine with it. Otherwise you'll fail your students as heretics and they won't get a job maybe. OK, but you are still twisting the reality to fit your dogmatic point of view - "the body as a hypoxic environment". A dead body yes. It's more complicated than you say. Oxygen saturation varies from point to point in the body, it's is not a strictly uniform O2 saturation everywhere but human cells respire aerobically in the body and to be able to do so then immediately outside each of those cells must be an oxygenated environment - the extra-cellular fluid must have good oxygen saturation for the cells to respire aerobically. That's an important fact which you are obscuring with your "hypoxic body environment" dogma. Maybe we should agree to disagree on our respective use of those words because I don't think either of us is going to change our minds or our language. I know I am not. Edited October 19, 2013 by Peter Dow
CharonY Posted October 19, 2013 Posted October 19, 2013 (edited) It's not the case that if you inject a strictly anaerobic bacteria into healthy tissue that the anaerobes can cause an infection at that location. No; healthy tissue is too well oxygenated for anaerobes to proliferate. So they'd just be dormant, just stuck in place doing nothing or circulating around until dealt with by the immune system. These kind of extrapolation are unfortunately the byproduct of partial knowledge on the subject. Anaerobic bacteria are a problem once they get in tissue, you do not need ischemia or anything for them to persist. Clostridia are one of the main problems after transplantation since their spores are so hard to get rid off. If they embed themselves nicely in tissue they can cause a lot of damage because, as everyone is saying here, the tissue is not really aerated. In fact, if OP's claim were true, clostridia or any other anaerobic pathogens would be unable to infect and kill their hosts unless the host had some sort blood vessel problems. This is simply ridiculous and ignores for example the well-known fact that many anaerobes are part of the normal human flora. They live in many parts of the body, including areas that appear to be well-aerated (mucous membrane of mouth and throat, for example). Again, the reason being that local oxygen concentrations are low (often due to biological activities). Heck, pulmonary infections are often cause by anaerobes including Fusobacterium and Bacteroides. Then there are the vast amount of intracellular pathogens that just live inside host cells. Why? Because there is not a lot of oxygen to go around. If you think carefully, the way the tissue is built up and limits to diffusion rate and the involved binding and release of oxygen to heme groups and compare it to respiration rates, it should become quite obvious that most of the body is, in fact not oxygen saturated. In summary, putting pathogenic bacteria deep into the body is calling for trouble, anaerobe or not. Edited October 20, 2013 by CharonY
John Cuthber Posted October 19, 2013 Posted October 19, 2013 "That's when gangrene is a problem because a major trauma, like having parts of your body pinned under something heavy for hours or getting shot in war, causes a massive quantity of your body tissue to lose its supply of oxygen and that is indeed a problem for the oxygen-deprived tissue - it is called ischemia -" or not, but Yeah, we know. Get back to me when you get to the bit where you realise that t it spreads to healthy tissue. Don't forget that this "It's not the case that if you inject a strictly anaerobic bacteria into healthy tissue that the ..." isn't relevant. You plan to introduce them to a tumour. Had you forgotten that that was the point?
Ringer Posted October 19, 2013 Posted October 19, 2013 I'd prefer to phrase it this way - the body cells are not hypoxic thanks to the functioning of the circulatory system. . . . ... and all of the cells of the body are well saturated with oxygen and not hypoxic, not in the least low in oxygen. So I have to ask, do you think the bacteria live inside the cell? Ah at last - a different question. How refreshing! The development of drug-resistant strains of bacteria depends on those strains being able to keep themselves going by spreading from patient to patient. The bio-agent reference samples will be stored in an isolated laboratory and will not be mutating in vitro in the lab and if any samples ever did, they'd be disposed of. The bio-agents to be used will be bred from the reference samples. They won't have time to mutate in-vivo before they are killed off before phase 2. In any case, if a patient jumps out of his bed after phase 1 goes home and in 20 years the bio-agent in his body has mutated to a drug resistant strain it matters not because we won't be breeding bio-agent from the bacteria in that ex-patient but from the reference samples in the laboratory. Your concern is as logical if you buy a pure bred puppy from a dog breeder but you are worried that other dogs might have escaped from the dog breeders kennels and have bred with other stray dogs to produce mongrels, not pure-breds. Well, so what, so long the puppy you get is a pure-bred you should be happy so quit your whining. You implying that criticism is analogous to whining really says a lot about now this thread has been going. Please do tell how you will keep them from becoming resistant other than just making a statement that they won't. Otherwise you'll fail your students as heretics and they won't get a job maybe. OK, but you are still twisting the reality to fit your dogmatic point of view - "the body as a hypoxic environment". A dead body yes. It's more complicated than you say. Oxygen saturation varies from point to point in the body, it's is not a strictly uniform O2 saturation everywhere but human cells respire aerobically in the body and to be able to do so then immediately outside each of those cells must be an oxygenated environment - the extra-cellular fluid must have good oxygen saturation for the cells to respire aerobically. That's an important fact which you are obscuring with your "hypoxic body environment" dogma. Well, they would get that question wrong because they can't understand the difference between internal and external environment. It's a pretty important distinction. Again, if the outside of the cell was well oxygenated the circulatory system would be unnecessary. Maybe we should agree to disagree on our respective use of those words because I don't think either of us is going to change our minds or our language. I know I am not. Well, since you now state that you will not change your mind I will happily wash my hands of this thread. But please keep in mind that reality isn't dictated by your belief.
Peter Dow Posted October 20, 2013 Author Posted October 20, 2013 (edited) You still seem to be having trouble with the fact that glycolysis (i.e. anaerobic respiration) is not equitable with a hypoxic environment. No one is debating that most cellular respiration is aerobic. However, for that respiration to take place, cells a need constant supply of oxygen delivered to them via the circulatory system. Without the circulatory system, aerobic respiration rapidly ceases. This is because the ambient oxygen level is too low for aerobic respiration to occur. This in turn means that the interior of your body is, you guessed it - anaerobic. That should also be evident to anyone whos studied basic biology. Well, in combination with the above it has clarified the fact that youre still having trouble understanding that cells respiring aerobically arent necessarily located in aerobic environments. As an extreme example, the multicellular organisms living in deep sea hydothermal vent communities, one of the most anaerobic habitats on earth, still have some aerobic cell respiration. http://link.springer.com/article/10.1007/BF00394718#page-1 Again, most of the interior of the human body is hypoxic (wiki link for basic definition http://en.wikipedia.org/wiki/Hypoxia_(environmental)) Otherwise you would not require a circulatory system for cellular respiration. Your argument is like saying "Without roads allowing people to drive cars, buses and lorries around cities, transport in cities would be impossible because cities are low-vehicle environments (hypo-vehicular)." No, cities are not "low vehicle environments". In fact they are well saturated with vehicles. By means of that analogy, I hope to make the point that yours is a misleading way of talking about all the oxygen which is available for the cells in our bodies. If you went around saying that cities were "low vehicle environments" they may not have you carted away to the funny farm if you were lucky but you'd find it very difficult to hold down a job teaching urban transport planning anywhere talking such nonsense. Yes there are some places in cities where cars can't get to - like there are some places in our bodies which oxygen can't get to. Overall though, the picture is of cars in cities and oxygen in our bodies. Cities are not low-vehicle environments and bodies are not low-oxygen environments. Well, perhaps not explicitly, but its been implicit throughout for example, the suggestion of antibiotics to control you agent infers that the agent will be a bacteria. Obligate anaerobe bacteria seem to be most promising for the bio-agent task. How will you do this? Bacterial susceptibility to antibiotics is highly variable, temporally and spatially in the same species of bacteria http://cid.oxfordjournals.org/content/32/Supplement_2/S114.short. If you could guarantee that your agent would not develop resistance to your antibiotic youd have solved antibiotic resistance. Given that antibiotic resistance has a massive burden on human health, overcoming this challenge to your proposal would both a) have a massive positive impact on human health independent of any cancer treatment. B) Represents a significant, currently unresolvable challenge to your proposal. Like I explained earlier, the reference strain of bio-agent is kept in a laboratory, where all kinds of strains of bacteria can be stored separately and keeping non-drug resistant strains away from drug-resistant strains. You simply run the laboratory well enough so that some idiot does not mix up the batches of one strain with the other strain. You put labels on the petri dishes saying things like. "DANGER! Drug resistant strain - do not use as a bio-agent!" Or you keep the drug resistant strains in another building because you can't trust the fools you've hired not to mix them up if they are stored in the same building. Is this so hard for you to understand? This has nothing to do with the development of drug-resistant strains of bacteria in the population. That's a separate issue. My treatment approach has nothing to say about the issue of drug-resistance because the bio-agent is not selected by taking samples from anywhere other than strictly controlled science laboratories and the lab would supply a strain which was not resistant to the anti-bio-agent drug it was paired with. If I want a drink of water I drink from the tap, I don't drink from the rainwater in a puddle on the street. I choose the pure sample of water. Likewise with the bio-agent, the doctors would choose the pure strain which presumably would be supplied by big pharma, along with the anti-bio-agent drug. Doctors would not go hunting for bio-agents themselves same as they don't go hunting for anything else they use in hospitals! Doh! Is this point so hard for you to understand? In your initial proposal you simply state that the patients immune system will take care of the agent. No mention of antibiotics to counter the infection. No that's not correct. I did mention use of an antibiotic in the this paragraph from my OP. Treatment Phase 1 It is proposed that phase 1 use a mild anaerobic biological agent (with the suggestion that this is mostly likely to be a selection of a mild, treatable, non-drug-resistant anaerobic bacteria, sourced from a well-characterised laboratory specimen) with which the cancer patient is purposefully infected and 1 type of drug, matched to be a known effective treatment capable in high doses of eliminating the selected bio-agent from the body or in small doses to moderate the intensity of the infection. Now maybe the penny did not drop for you that I was talking about an antibiotic when I used the word "anti-bio-agent drug"? It looks like I did not use the word "antibiotic" until my post #26. The approach would be to expect a tendency for there to be side-effects and to manage the infection with the anti-bio-agent antibiotic drug which is integral to phase 1 treatment so as to reduce the systemic side-effects and local side-effects on particularly vulnerable sites in the body right down to acceptable and tolerable minimal side-effects. But I was always talking about an antibiotic when I used the word "anti-bio-agent drug". But, specifically I was talking not about just any old antibiotic picked from the shelf at random but one selected for use as part of the pair of phase one treatment tools - the bio-agent and the anti-bio-agent drug (maybe supplied as a twin pack by big pharma). Is that clear for you yet? As pointed out, simply relying on the immune system would likely fail, as any biotic infection which is easily contained by the immune system doesnt spread throughout the entire body, and any infection which spreads throughout the entire body rather by definition isn't contained by the immune system. Well the idea would be to saturate the body with too much bio-agent for the immune system to mop up before the bio-agent got its spores or whatever so widely distributed that the body could not stop the spores germinating in hypoxic cores in due course. But that'll be a spread of the inactive form of the obligate anaerobe - that doesn't mean a wide-spread living infection that is harming the body and which the immune system, or you on the patient's behalf, needs to be too worried about. I also feel that youre doing an excellent job of demonstrating why a lot of posting experience in forums isnt a substitute for a solid fundamental understanding of the given topic at hand. I do understand the topic. I also know that others do not understand me. That's a communication problem. I am working on it, but it is not easy. Overwhelming the immune system with a massive, systemic infection of an agent which attacks all hypoxic tissue is commonly known as sepsis, and is commonly fatal, almost always leaving permanent, systemic organ damage. http://www.nlm.nih.gov/medlineplus/ency/article/000666.htm No "sepsis" means a different kind of "overwhelmed" immune system. Sepsis means a very active immune system responding to what is perceived by the immune system to be a rampant, very severe infection. In my approach, the distribution of a large enough number of spores etc. around the body does not mean a severe infection. It will be a mild infection with a fairly harmless anaerobe. Now, of course there is always a danger of an over-active immune system. Some people have allergies and some people might develop an allergy to the bio-agent spore, if indeed spores are used. OK so there is a job for the intensive care to manage an inappropriate immune response - using anti-histamines or whatever. It's manageable. As has been stated, if your entire audience has a misconception, the most likely explanation is that you are not explaining clearly, or the audiences misgivings with your presentation are actually genuine rather than misconceptions. Well I've always had difficulty explaining what for me are simple matters to the less gifted. It is very frustrating for both parties no doubt and thank you for your patience. To quote you verbatim: [/size][/font]Oh my approach doesn't require "modifying" bacteria. My OP didn't mention "modification" of bacteria to do anything other than what comes natural to bacteria. I've answered this point recently in post #65 in reply to Ringer. I did say that but that was in response to someone claiming I was looking for, can't remember the exact words, something like "magic" bacteria, whereas, no, it is simply selecting the best for the bio-agent job which are available from obligate anaerobes, whether native or genetically-modified strains. The point I was making was that what is required for the bio-agent is not some mythical beast but the most suitable out of what is there and so by all means pick an existing genetically-modified strain like Clostridium novyi-NT if tests prove that to be the most suitable when compared with the 100s of native obligate anaerobes out there. I was just making the point that the behaviour required from the bio-agent desired is characteristically typical behavior, not at all science fiction. I am now including a link to Wikipedia articles about Clostridium novyi-NT in the latest versions of my OP posted elsewhere because that often comes up in discussions, but my approach is in no way founded upon that GM strain, as if the approach would fail without that strain. Apologies maybe it would have been clearer for me to have said pathogenic rather than toxic. The point was that carefully administering local treatments with high toxicity/pathogenicity to specific, affected parts of a body, as the C. novyi/radiation example provide, doesnt in any way provide evidence that the administration of these agents systemically would be effective. In fact, their efficacy is in both cases brought about by their toxic/pathogenic properties - which if administered systemically would kill a patient. Well the bio-agent can only thrive by killing and consuming human cells and debris where it is hypoxic, where those human cells cannot respire aerobically, where the bio-agent must respire anaerobically. In its inactive form, the bio-agent is spread around the body yes. But it is only activated where the local environment is hypoxic, and that's not where the living cells are. Well, no. A host of anaerobic pathogens are quite effective at attacking healthy tissue. Even microbes which for the large part, like S. aureus, E. coli and P. areuignosa exist on and around us without causing any damage can become serious pathogens in the right conditions The sole example of a bacterial cancer treatment will cause gas gangrene in the right conditions. You are describing a bio agent with a rather remarkable phenotype the likes of which I would speculate doesnt actually exist in nature. However, it seems like your proposal, and subsequent defense of it simply assume it will be there. Precisely, "in the right conditions" and those conditions only apply so far as the bio-agent is concerned, in hypoxic tumour cores where a large feast of easy meat is awaiting the obligate anaerobe to dine on. [*Im not a student. This fall semester represents the second time Ive co-taught introductory anatomy.As explained above, the majority of the human body has an oxygen level lower than air. This is the reason you require a circulatory system to deliver oxygen to your cells. If the ambient oxygen level I the human body was aerobic, red blood cells would have no purpose. Quite. I do understand. I think you understand the reality of the body as well but your choice of language at times I find to be inappropriate and not helpful. Edited October 20, 2013 by Peter Dow
Arete Posted October 20, 2013 Posted October 20, 2013 Your argument is like saying "Without roads allowing people to drive cars, buses and lorries around cities, transport in cities would be impossible because cities are low-vehicle environments (hypo-vehicular)." Congratulations, with this nonsensical analogy we've just achieved the level of crackpottery known as "not even wrong" ' Is this so hard for you to understand? I now fully understand that you don't understand what antimicrobial resistance is. 1
Phi for All Posted October 20, 2013 Posted October 20, 2013 ! Moderator Note Thread closed pending staff review.
Phi for All Posted October 20, 2013 Posted October 20, 2013 ! Moderator Note After staff review, it's been decided that the thread will remain closed. 3
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