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Bad Books

In the interests of fairness and intellectual honesty, I’ve forced myself to read a lot of really bad books. The True Believer tells me his guru’s book is the Real Stuff. He tells me I have a closed mind and won’t look at anything outside establishment dogma, and if I only read the book and understood Dr. Quack’s evidence and arguments, I would be a True Believer too. I have tried, really I have. I’ve given the Dr. Quacks every chance to convert me, and I’ve hoped to learn something new, but I’m always disappointed. I’ve come to the point that I feel like I’m reading the same book over and over: it is always a mixture of real science, pseudoscience, and speculation, based on cherry-picked evidence and argued with the same logical fallacies.

I recently got hooked into reading another one by a correspondent who had called me an “ignorant relic” for writing a “grossly ignorant article” about alternative medicine. I suggested he read R. Barker Bausell’s book Snake Oil Science and a couple of others, which he promised to do. Then he said, “If I am willing to buy three books that you have suggested and read them and you are not willing to read what I have suggested, then that pretty much says all that needs to be said.”

I was willing, even though the very title of the book suggested that its message was incompatible with the scientific evidence as I know it: How to Prevent and Treat Cancer with Natural Medicine. The authors are big names in naturopathic and herbal medicine: Michael Murray, Tim Birdsall, Joseph Pizzorno, and Paul Riley. It’s nowhere near as bad as some of the bad books I’ve read, but it is a good example of the genre and I’ll use it to illustrate why I call them bad.

It offers “an arsenal of disease-fighting tools for prevention, treatment, and coping with side effects” (Yes, it offers tools; but do those tools work?) And it promises to “change your internal environment so cancer can’t survive.” (Wow! If it could really do that, every oncologist in the world would enthusiastically adopt these methods and the authors would be eligible for a Nobel prize.)

Its coverage of cancer risk factors and screening tests is reasonable, and it doesn’t discourage conventional cancer treatment. It recommends conventional preventive measures like exercise, weight control, and healthy diet, and points out the need for extra attention to good nutrition during cancer treatment. It doesn’t descend to the level of Andrew Weil’s promotion of “stoned thinking” and intuition as a source of knowledge. It appears to be grounded in science and its recommendations are evidence-based. The problem is that it accepts evidence of exceedingly poor quality, and it accepts evidence that has been superseded by other contradictory evidence (which it conveniently fails to acknowledge).

A trivial example, but one that illustrates their loose approach: they tell us acupuncture dates back 5000 years to The Yellow Emperor’s Classic of Internal Medicine, attributed to the emperor Huang Ti in 2697 BC. They don’t mention that modern scholars have determined that the book was written much later, probably in the second century BC. The older date enhances their claim that

TCM [Traditional Chinese Medicine] has been practiced for millennia, longer than any other medical system. There must be something valuable in it! [Logical fallacy]

They fully accept the claims of TCM. They fail to mention that the so-called acupuncture meridians have never been detected, and they speak of the mythical qi as if it were as real as blood pressure. They accept the totally unsubstantiated concept of “energy medicine.” They think there is no fundamental clash between Western medicine and TCM, that just as light can exist as particles or waves, health problems can affect both chemical balance and energy balance. [false analogy]

They state

External hydrotherapy treatments have been shown to produce profound effects on immune function. In particular, applications of hot water have been shown to boost the number and activity of natural killer cells – key white blood cells in the fight against cancer.

As a reference, they cite this study. This was a preliminary study with only 10 subjects and no controls, and the number of NK cells only increased in 5 patients. A search of PubMed yielded only one other study of hydrotherapy and immune function, this one also uncontrolled and involving only 11 subjects.

You would have to put on the strongest rose-colored glasses to interpret these two questionable studies as evidence of “profound effects.” And that is exactly what these authors do throughout the book. Their rose-colored glasses over-interpret the significance of every study that supports their bias while they filter out any contradictory information.

They state that faith and the power of prayer have been “validated by several rigorous scientific studies” showing that prayer affects everything from the mutation rate of bacteria to the size of tumors. This is simply not true. Claims for the medical efficacy of prayer have been repeatedly and thoroughly debunked. Yet these authors say,

In our opinion, given the scientific support of prayer’s beneficial effects, not praying for the best possible outcome may be the equivalent of deliberately withholding an effective drug or a surgical procedure.

They stop short of advising us which God to pray to.

For patients undergoing surgery, they say “It is very important to use gotu kola to prevent the formation of adhesions.” They say it has “demonstrated impressive clinical results in promoting wound repair.” The Natural Medicines Comprehensive Database, after reviewing all the published studies on gotu kola, concluded that it is “possibly effective” when used topically for wound healing and prevention of keloids, and “possibly safe.” I couldn’t find a shred of evidence anywhere that it can prevent the formation of adhesions internally. As far as I can tell, the authors just made that up, extrapolating from the idea of wound healing.

For cancer prevention, they recommend everyone take 17 supplemental vitamins, 14 supplemental minerals, flavonoids, daily green drinks (green tea, dehydrated barley grass, wheat grass, chlorella, spirulina), probiotics, fish oil supplements, and for extra protection against specific cancers, curcumin, quercetin, ground flaxseed oil, lycopene, etc. The evidence to support these recommendations is sketchy at best (I’m trying really hard to say this politely).

I’ll stop with these few examples. It would take a book twice as long as theirs to properly critique all their questionable statements.

This book is a strange mixture. It contains a lot of good science and good advice, but it also contains statements that are clearly false, and much of it consists of unjustified extrapolations from preclinical or preliminary studies. It unwisely makes clinical recommendations for the entire human population on the basis of a few animal or in vitro studies.

It epitomizes the difference between “evidence-based” and true science-based medicine. It is easy to find studies that serve as “evidence” for any viewpoint, but the true scientist weighs those against other contradictory studies, assesses the study design and the quality of evidence, asks if the data have been replicated elsewhere, looks at prior plausibility and compatibility with other scientific knowledge, and tries to judge what the entire body of scientific evidence means. As Ioannidis showed in his landmark article, most published studies are wrong.

The book has the appearance of science and authority and it cites lots of references. It is written to impress the general public, and I’m sure it sounds very convincing to someone who is not well versed in the subjects covered. But its defects are obvious to anyone who truly understands the scientific method. The authors have an obvious bias; they are not objective, some of the things they say are demonstrably false, and the book is not a reliable source of information or advice.

There are two kinds of science book: one aims to educate the public by explaining the current state of evidence and the consensus of the scientific community. The other has an agenda: it uses (and mis-uses) science to persuade readers to believe something that the authors believe but that the scientific community as a whole has rejected. I have learned to tell them apart at a glance. Unfortunately, the general reader hasn’t.

Caveat emptor and caveat lector.

Posted in: Book & movie reviews, Herbs & Supplements, Science and Medicine

Leave a Comment (27) ↓

27 thoughts on “Bad Books

  1. Michelle B says:

    If anyone should read these bad books, it needs to be someone like you, knowledgeable and able to analyse the logical fallacies, refute the so-called proof, and publish your rebuttal on this blog.

    A somewhat intriguing interpretation why we are now so focused on probiotics, super fresh produce, organic items, is because we need to be righteous about something (sexual attitudes used to take this emphasis). How much difference nutritionally is there between fresh food and canned/frozen food? Apparently so much, one can cure disease! (http://www.hoover.org/publications/policyreview/38245724.html

    The proponents of quackery must also be paranoid. As you said, if these approaches are as powerfully curative as stated, then why not are they embraced by all medical doctors? They prefer to think that the reason is because the medical doctors want to keep their status quo so much that they will opt for letting people die. Though there certainly are doctors who do focus on making lots of money, in general, the challenge and attraction for many doctors is to treat and cure disease and maintain health.

    As it is said, if someone reaches a conclusion not based on reason, that person will then resist reason in order to let go of his/her misconception. Hence the long, hard battle against quackery.

  2. daedalus2u says:

    A comment on hydrotherapy. Many thermal springs (and virtually all other natural water sources) contain ammonia oxidizing bacteria. Bathing in such a spring would be expected to inoculate the skin with these bacteria. They are motile, and so presumably move in a chemical gradient to maximize their access to the substrates they need (ammonia). Presumably bathing in water containing these bacteria would inoculate the pores where these bacteria would generate NO and nitrite from normal ammonia release.

    NO is highly involved in immune system regulation and has anti-inflammatory effects by inhibiting NFkB and reducing mast cell reactivity. My research suggests that humans evolved with a biofilm of these bacteria on their skin, and removing that biofilm has adverse health effects due to the loss of the NO and nitrite that they produce in response to release of ammonia via sweating (thermal and non-thermal).

  3. weing says:

    It is amazing how these people would not accept a pharma sponsored study with 11 subjects and no controls as evidence of efficacy and safety, and rightfully so, but will not bring the same skepticism and demand for evidence to studies of hydrotherapy and other quackery.

  4. Michelle B says:

    “…that person will then resist reason in order to let go of his/her misconception.”

    I meant resist reason in order to keep his/her misconception.

  5. qetzal says:

    deadalus2u,

    I can no longer resist commenting on your impressive perseverence in linking almost everything to NO. With all due respect however, I find a disturbing woo-like quality in many of your comments. Specifically, you seem to think that NO is causally involved in almost every major disease, and that restoring proper NO metabolism will help treat or cure most such diseases. This reminds me of people who think their favorite woo is the key to curing all disease. In fact, one of your blog posts states “As we all know the secret to good health is NO.” I assume that was at least partly tongue-in-cheek, but it seems like a pretty good summary of most of your comments.

    Of course, we know that NO is a real molecule with real physiological effects, but isn’t it a bit of a stretch to claim as broad a role as you do? Your arguments frequently assume the truth of what appear to be unproven assumptions at best. At least, that’s been my impression.

    Taking your latest comment as an example:

    Many thermal springs (and virtually all other natural water sources) contain ammonia oxidizing bacteria. Bathing in such a spring would be expected to inoculate the skin with these bacteria…Presumably bathing in water containing these bacteria would inoculate the pores….

    It’s quite a leap to go from mere skin exposure to presuming actual inoculation of the pores. My understanding is that most bacterial species will not colonize skin even if given the opportunity. Why should we presume that ammonia oxidizing bacteria would do so?

    My research suggests that humans evolved with a biofilm of these bacteria on their skin….

    I searched PubMed for any indication that ammonia oxidizing bacteria are ever found on the skin of any animal. I couldn’t find any. If humans truly evolved with such biofilms, then their ancestors would also have had such biofilms, and we should expect to see them in other mammals (or at least other primates). Can you point to any research that supports your claims?

    I looked at your blog to see if you address any of this in more detail, but couldn’t easily find anything relevant. If there is a post or label category where you provide more support for all these claims, I’m happy to look at what you’ve already written.

  6. apgaylard says:

    Harriet: Nice post. I do think that you’ve perhaps been a tad hard on EBM when you say:

    It epitomizes the difference between “evidence-based” and true science-based medicine. It is easy to find studies that serve as “evidence” for any viewpoint, but the true scientist weighs those against other contradictory studies, assesses the study design and the quality of evidence, asks if the data have been replicated elsewhere, looks at prior plausibility and compatibility with other scientific knowledge, and tries to judge what the entire body of scientific evidence means.

    Although I’m a layman I would say that I’ve seen EBM-type analyses which do all of the above except consider, “prior plausibility and compatibility with other scientific knowledge”; which I know is a substantial fault. However you will see plenty of the other behaviours in meta-analyses and reviews.

    Even R. Barker Bausell’s distinctly EBM approach to CAM includes criteria that would separate most of the chaff:

    “Give more credence to trials published in well known medical journal and give no credence at all to those published in CAM journals.

    Give more credence to trials conducted in English and Scandinavian language speaking countries. A systematic review published several years ago found that investigators from certain countries (most notably China and Russia ) produced only positive results in their acupuncture trials.

    Did the trial employ a randomly assigned placebo-sham control group indistinguishable from the therapy being evaluated?

    Did the trial employ at least 50 participants per group?

    Did 25% or more of the participants drop out of the study before it was over? “

    His yardstick of 50 participants/group would rule out many of the studies cited in your “Bad Books”.

    But perhaps I’ve got the wrong end of the stick and “evidence-based medicine” isn’t being equated with EBM?

  7. daedalus2u says:

    qetzal, you are correct, there isn’t anything published on this yet. As far as I know, I am the only person doing research with these bacteria as commensal organisms. I have found them living on the surface of multiple eukaryotes, vertebrates and invertebrates. I have some unpublished data I could send you.

    I have had a stable biofilm of these bacteria growing on my skin for over 7 years now. These bacteria are non-culturable with the techniques used for isolating pathogens or heterotrophic bacteria. There are some non-culture techniques that are starting to be used that are showing the presence of these bacteria in various tissue compartments. The recent post at Sandwalk on bacteria in the mouth showed they are present.

    I have instrumental measures of NO production by these bacteria in vivo (human) coincident with instrumental measures of a physiological effect known to be mediated by NO. I appreciate that it is an n of 1 (but on multiple instances) and so is considered an “anecdote”, even though the measures are all instrumental and at many sigma above background.

    I have presented at multiple nitric oxide conferences (and on the opening night of a Gordon Conference on NO) and have been well received, but so far only 1 researcher has been willing to collaborate with me and we have not yet been able to get sufficient funding to do tests on additional subjects.

    People seem to either think they can’t possibly be important, or that they must be harmful. Without data showing they are “harmless” (even though there has been no report of infection by them, they contain no genes for any virulence factors and are incapable of growth on any media used to isolate pathogens) people think they must be harmful.

    Without a lot of data I can’t get funding and without funding I can’t get a lot of data. I happen to have a low NO physiology, which I inherited from my mother. She and both her parents died with advanced Alzheimer’s. I am sure I got my low NO physiology from them. The changes I have observed have been remarkable. I appreciate that my observations are anecdotes. I appreciate that most people consider my observations to be due to the “placebo” effect. In virtually all cases, my observations preceded my understanding of the involvement of NO in those physiological pathways. My hay fever went away before I knew that NO regulated the immune system via NFkB and other pathways. My Asperger’s got better before I knew I had Asperger’s. My metabolic syndrome got better before I understood the mechanism by which low NO causes the metabolic syndrome. My liver enzymes went down before I understood the mechanism by which NO lowers liver enzymes and before I thought to measure them during the course of my “experiment”. I noticed more frequent nocturnal erections before I knew that the mechanism for erections was through NO.

    With the understanding that all NO sensors only sense the sum of NO from all sources, the basal level of NO becomes a critical part of each and every NO pathway. There are hundreds, or thousands of NO pathways. Lowering the basal NO level skews each and every one of those pathways in a characteristic way, in the same way as does “stress”. Essentially every disease exacerbated by stress is exacerbated by stress because stress causes low NO. There is no threshold for a change in basal NO to change the operating point of each and every pathway. NO is already an active regulatory molecule. A change in the basal NO level will produce a change in the output of those pathways.

    I understand that what I am saying sounds like woo to those who don’t understand it. I think that once someone does understand NO and these bacteria the way that I do, they will come to the same conclusions. But the amount of background one needs to understand to reach that same conclusion is not small, and without understanding that it is correct, the motivation to acquire that background isn’t present. I am not quite hyperlexic. I can read technical material extremely rapidly. The amount I have read and understood is not small. All of it is consistent with the hypothesis that these bacteria are important in human physiology.

  8. LindaRosaRN says:

    I supposed this book is the basis for the creation of the specialty called
    “Naturopathic Oncology”:
    http://www.oncanp.org/

    Thanks for the review.

  9. tmac57 says:

    Dr Hall, nice review. I went to Amazon to check out how it was selling, and only found one 1 star review out of 18 reviews, and that was a repost of your article here. the others were two 4 star, and fifteen 5 star reviews. It was also rated at #82 within it’s genre.
    For all of the blog readers here, why not browse over to Amazon and rate the 1 star review as most helpful if you agree with Dr Hall’s analysis. SBM needs all of the voices we can muster.

  10. daijiyobu says:

    Dr. H.:

    you may be interested in the op-ed piece published in the Vancouver Sun yesterday

    “Endorsing Naturopathic Medicine Accepts Science Over Spin”

    per http://www.vancouversun.com/Health/Endorsing+naturopathic+medicine+accepts+science+over+spin/1347334/story.html .

    BCNA president Kind makes some very SOLID claims concerning naturopathy’s [bogus] science-expertise!

    A sample:

    “the science behind naturopathic medicine is substantiated by voluminous [!!!] research conducted by independent, third-party medical experts. In fact, the science behind naturopathic and standard medicine is not different [!!!]; it is the philosophy behind the application of that science that differentiates naturopathic doctors (NDs) and medical doctors.”

    And what is the science behind the philosophy behind the science that justifies the philosophy guiding the science that is philosophically basing the scientific basis of naturopathy [etc.]?

    Another sample:

    “[we've displayed] comprehensive knowledge in biological and biomedical sciences.”

    So, NDs are such science-experts that:

    naturopathy can claim that PROFOUNDLY science-unsupported [or -ejected!] articles of faith such as ‘purposeful life spirit bioagencies, akin to god within oneself’ [their philosophy {autoentheism, vitalism, spiritism, teleology & kind}] survive serious scientific scrutiny.

    A final sample:

    “the scientific education and training that naturopathic physicians receive is no different than the scientific training medical doctors receive [{except for the fact that figmentations and premises decades and a few hundred years science-discarded are considered by us as currently scientific!!}...] naturopathic students receive more training in basic and some clinical sciences at accredited naturopathic colleges than that offered at some standard medical schools [{their superscience claim!!!}...naturopathy is] quality, science-based health care.”

    And their science-expertise is obvious, after one appreciates how completely the science-exterior is, for naturopathy, considered to be the same as that which science legitimately supports / bases.

    -r.c.

  11. clgood says:

    My research suggests that humans evolved with a biofilm of these bacteria on their skin, and removing that biofilm has adverse health effects due to the loss of the NO and nitrite that they produce in response to release of ammonia via sweating (thermal and non-thermal).

    So… I shouldn’t bathe? Or could I just smear on NO lotion afterwards?

  12. shawmutt says:

    In addition to “Bad Books”, bad websites are equally foolish. It’s really silly–these remedies attempt look like the real thing, and have mastered the art of using a lot of “sciency” words to make it look like real science. The internet gathers these wonks and faith-based medicines together and helps them last much longer than they should.

    One example that is again gaining ground is the homeopathic remedy Oscillococcinum ( http://www.oscillo.com/ ). This website is so slimey and slippery and can convince a lot of folks lacking in critical thinking skills. In the end, it’s a sugar pill, like most homeopathic medicine probably doesn’t contain a single molecule of the supposedly helpful component, and is based on a thourougly debunked idea. The “proof” that it works is contained in a 10-year old study published in a homeopath-specific publication and a 20-year old study.

    But it has studies! And the FDA calls it a drug! And it has warnings like “keep out of reach of children (lol)! And millions of people take it!

    I’m just glad you have the patience to read some of the plethora of Bad Books out there, I’m too fed up with the bad websites to want to waste money and fund quacks and wackos.

  13. daedalus2u says:

    clgood, yes, exactly. Once you have the right biofilm you don’t need to bathe. Our ancestors in Africa didn’t bathe for millions of years. We evolved to have a biofilm of these bacteria on our bodies and when that biofilm is removed our physiology loses an important regulatory pathway (generation of NO/NOx via sweating) and becomes dysregulated. That dysregulation is in the “fight or flight” direction, so you can actually “feel” like you have more energy, like you are “refreshed”. That is due to the activation of stress pathways.

  14. tmac57 says:

    daedalus2u:”That dysregulation is in the “fight or flight” direction,..” No wonder that it is so hard to get kids to take a bath!!! Just say NO to bathing!!!

  15. Dr. Hall’s findings about this book’s references to “scientific studies” are similar to my own regarding other naturopathic treatises. For examples from the AANP Position Papers and the Textbook of Natural Medicine (the only ‘textbook’ of ‘naturopathic medicine,’ edited by Pizzorno and Murray), look under #3 here:
    http://www.medscape.com/viewarticle/471156

    And in SBM here:
    http://www.sciencebasedmedicine.org/?p=151

    For a critique of “the scientific education and training that naturopathic physicians receive” (see the quote in daijiyobu’s comment above), look under #4 in the Medscape article linked above.

    That article, by the way, was in response to angry letters that followed this article:
    http://www.medscape.com/viewarticle/465994

    One of those letters had been written by Yale’s David Katz:
    http://www.medscape.com/viewarticle/470713

    Notice that Katz gives himself credit for having published a “textbook on principles of evidence-based medicine.”

    Veteran SBM readers will recognize Katz as having recently opined that disconfirming trials of implausible claims are “an invitation to think more fluidly about evidence”:
    http://www.sciencebasedmedicine.org/?p=167

    The authors of the book Harriet reviewed, by the way, are representative of the highest levels of ‘naturopathic medicine.’ Pizzorno past president of Bastyr University (the most conspicuous school) and is also one of two appointees to the Medicare Coverage Advisory Committee in 2003, which precipitated my critical article. I’ve previously discussed Murray here:
    http://www.sciencebasedmedicine.org/?p=146
    and in the SBM article linked above.

    Timothy Birdsall is Vice President of Integrative Medicine at Cancer Treatment Centers of America (CTCA), an organization that apparently ‘integrates’ snake oil with medicine:
    http://www.cancercenter.com/western-hospital/doctors/timothy-birdsall.cfm

    Paul Riley is National Director of Naturopathic Medicine at CTCA:
    http://www.cancercenter.com/seattle-clinic/physicians/paul-reilly.cfm

    Such examples show that quackery is the mainstream in ‘naturopathic medicine.’

    KA

  16. shawmutt says:

    Hippies hate water! Hippies hate water!

    http://www.youtube.com/watch?v=Dl5yJoeFLiQ

    Yeah, our ancestors in Africa only lived 20-30 years. I think I’ll stick to bathing.

  17. Newcoaster says:

    daijiyobu
    The recent Naturopathy debate in The Vancouver Sun has been interesting (they even published one of my anti-naturopathy rants!) The problem with the media is their idea of “fairness” is to give equal time..or column inches…to opposing points of view, without respect to the strength of the argument or the evidence behind it.
    The Minister of Health in British Columbia is clearly anti-science, or at least, he sounds about as well versed in science as Senator Tom Harkin.

    Harriet…thanks for reading books like this, so I don’t have to.

  18. daijiyobu says:

    Newcoaster:

    yes, ‘fairness policy’ is quite the wedge for all kinds of absurdities to claim an equal footing when compared to rational, evidence- and science-based knowledge.

    The ‘ethical code of journalism’, though, has this as its foremost principle

    (see http://www.spj.org/ethicscode.asp ):

    “seek truth and report it [...] members of the Society of Professional Journalists believe that public enlightenment is the forerunner of justice and the foundation of democracy.”

    There’s something quite wrong with ‘fairness’ when it is basically distortion…

    something quite Orwellian [endarkening, unjust, undemocratic etc.].

    I guess there’s some kind of doublethink pun in the title “Minister of Health”, when health is no longer based on rigorous, modern, scientifically-derived knowledge.

    -r.c.

  19. qetzal says:

    deadalus2u,

    Thanks for the detailed response.

    Just to clarify, my reservations about some of your statements aren’t because I don’t understand them. I think your ideas are interesting as hypotheses, and some may well be correct.

    What catches my attention, and what I am respectfully objecting to, is your tendency to ascribe near certainty to your ideas, when they are really only hypotheses (at best).

    At least, that’s the way many of your comments seem to me. E.g., in your reply to me, you mention your “low NO physiology.” Is that a recognized state? Googling the phrase only turns up other comments by you, wherein you make claims like “I now understand that much of my depression was due to my low NO physiology (which I have now fixed). That is ultimately what leads to the vascular rarefaction that is associated with vascular depression (and all the other things associated with hypoperfusion in the brain).” (link)

    I seriously doubt that any of those claims are well supported. Rather, I think you merely speculate that you have something called ‘low NO physiology’ that you speculate you have now fixed, and that you speculate leads to vascular rarefaction, etc. I don’t think you can establish any of that to a reasonable scientific certainty, just like you haven’t established to a reasonable certainty that AOB biofilms on your skin had any of the effects you discuss in your comment above.

    It’s all speculation & hypothesis, but you typically write about it as if it’s virtual fact. The above-quoted passage is a case in point. To be honest, that kind of thing bothers me even more in a scientist than it does in a lay person. That’s why I couldn’t resist commenting.

    All that said, I would be interested in knowing a bit more about your AOB work. Specifically, how are you detecting AOB on vertebrate skin? I’d also be interested to know more of your experiments linking NO production by AOB on your skin with physiological changes caused by NO. If you’re willing to provide more detail, please email me at qetal -atsign- yahoo -dotcom-.

  20. qetzal says:

    Oops! That should be qetzal -atsign- yahoo -dotcom-.

  21. daedalus2u says:

    I detected the AOB by measuring increased NO (via chemiluminescence) when I added NH4Cl. The amounts I measured were many sigma above background and there were a couple of organisms I couldn’t detect any NO from. That actually surprised me. The instrument I used has a detection limit and resolution of less than 1 ppb. I was using air with zero NO background (normal ambient is 5 to 20 and is variable. The animal I found with the largest biofilm was a lobster, where I measured 500 ppb and the level was still going up. That was on a living lobster.

    To me, everything that has not been contradicted by reliable data is a “hypothesis”. No matter how confident I sound of a statement, it is still a hypothesis and I would be willing to abandon it or modify it if there was data that refuted it. If there is reliable data that refutes something, then it is simply wrong and isn’t a hypothesis any more.

    I am not alone in my appreciation of basal NO levels being important. There are a couple of other researchers, George B. Stefano is really the one who has been “preaching in the wilderness” about basal NO levels. His involvement preceded mine. It was reading his work that allowed me to formulate many of my own ideas. I have spoken with him, and we are (as far as I can tell) on exactly the same page. Slightly different emphasis, me on the bacteria, him on neurogenic production via relaxation response type things. His work does not get the recognition in the NO research community that it deserves.

    Multiple people have hypothesized that low NO is involved in many of these disorders. All I did was find the mechanism that had been supplying it, that modern living removed. People didn’t have a mechanism, and have been too enamored with fads about diet, antioxidants and genes.

    The wrong idea of homeostasis has also held back progress. There is no such thing as homeostasis. It is a wrong idea that needs to be abandoned. I blogged about that a year ago. Physiology is extremely well regulated. Physiology is not regulated to keep things “constant” as the wrong idea of homeostasis posits, physiology evolved to preserve the life and reproductive capacity of the organism. If the life and reproductive capacity of an organism is preserved by changing a parameter, then the organism will evolve to change that parameter.

    The other important contribution I have made is the realization that there is no threshold for changes in NO levels to affect physiology. NO is already a regulatory molecule. Changing the NO level changes the output of pathways that are already using NO as a signaling molecule. If you change the NO level you change those pathways. They can’t “compensate” because it is the compensatory pathways that are affected.

  22. daedalus2u says:

    qetzal, I thought of an analogy, which might explain the level of confidence that I have. Suppose that no one had the idea of evolution and common descent until the present time, but that all the data that is used to explain and “prove” common descent had been collected, just no one had put it all together. Suppose that the DNA of extant organisms had been sequenced, everyone knew that there were these similarities, that even non-coding sequences were conserved between organisms. The first person who put all the data together using the idea of common descent would be able to assert the hypothesis of common descent with the degree of certainty that we now have because he/she would have access to the same data and the hypothesis that unifies it all.

    The second person (the next person the first person tries to explain it to), might not understand it because he/she doesn’t have access to all the data and doesn’t have all the data in mind and so doesn’t see how the hypothesis of common descent unifies all the data, explains all of it, both what is seen and what is not seen. That there is no datum inconsistent with the hypothesis of common descent might be missed by someone not immersed in the data.

    The idea of common descent was a new paradigm that explained the data and relationships between the data in great detail and with great precision. New paradigms are sometimes very difficult for people to understand and accept. Millikan had great difficulty accepting that Einstein’s photoelectric effect was “real”, even though it was Millikan’s own data that had convinced virtually everyone else.

    The piece I sent you on Alzheimer’s provides what I think is a unified explanation of Alzheimer’s which is consistent with everything that is known about Alzheimer’s. It explains things that the amyloid hypothesis doesn’t, why trauma to the brain leads to Alzheimer’s, why there is reduced metabolism of the brain, why Alzheimer’s is characterized by buildup of damaged proteins, why clearing amyloid out via immune system stimulation doesn’t improve symptoms, why there is hypoperfusion, why there is considerable variability in the course of Alzheimer’s both in an individual and between individuals, why remaining mentally active helps (neurogenic production of NO), the oxidative stress observed (a low NO state is a state of oxidative stress), why some drugs of abuse (such as amphetamine) cause neurodegeneration themselves. It explains why there is no “smoking gun” of a genetic defect associated with Alzheimer’s. There isn’t a genetic defect. The physiology of the Alzheimer’s brain is operating “correctly”, it is simply operating with a bad “set-point”. The ATP setpoint of the brain is regulated by NO (as is the ATP setpoint in all tissue compartments). When NO is low, ATP is lowered as a physiological response. That is the “correct” response. There are billions of years of evolution that have caused physiology to respond that way.

    When there is low ATP, cells go into ATP conservation mode, what is called ischemic preconditioning. That ATP conservation is done internal to each cell. Each cell regulates its own ATP level. In Alzheimer’s, all the cells of the brain have the same metabolic rate, the same ATP concentration; they are all working “in sync”. A “defect” model would predict independence of defects of cell metabolism. This is not observed. All the cells in the brain seem to be working “together”. This is what I call good regulation around a bad setpoint. Ischemic preconditioning has been triggered, but the cells can’t “stand down” from that stress response because the “standing down pathway” is triggered by an increase in NO, and there isn’t enough NO to do that. That is where my bacteria come in. They increase the NO level a little bit, from perhaps 0.5 nM/L to maybe 1.0 nM/L (I don’t know the precise levels and the levels probably are not precise, but they are on this level (levels that are extremely difficult to measure in vitro, impossible to measure in vivo on the time, concentration and length scales known to be important)). That slight increase allows the brain to switch from the ischemic preconditioned state back to the normal state. The ischemic preconditioned state is analogous to the fight or flight state. Healing and repair is turned down/off to conserve ATP. To slow degeneration, that healing has to be turned back on. That is what a few nM/L of NO will do, switch the state of the cells back into the normal state where they can repair themselves (provided the damage hasn’t gotten too severe).

    I am pretty sure that essentially all of the common disorders that are called “complex genetic disorders” are not disorders at all, but are physiology operating correctly but with a bad setpoint. How can you have common disorders that are emergent properties of many genes? Common disorders must have common pathways.

  23. Dr Benway says:

    The first person who put all the data together using the idea of common descent would be able to assert the hypothesis of common descent with the degree of certainty that we now have because he/she would have access to the same data and the hypothesis that unifies it all.

    Um… no. Connecting the dots in an elegant way is not enough.

    You still must take some risk with your explanatory model before you are justified in granting it scientific merit. You have to predict some finding –without any peeking– then go look to see if you’re right.

  24. Dr Benway says:

    forgive my blockquote goof

  25. daedalus2u says:

    Dr Benway, no, the validity of a hypothesis does not depend on the degree of “risk” that the person putting it forward has been willing to subject themselves to. I agree that many people, scientists (and funding agencies) feel and act that way.

    When data is very sparse, producing new data to fill in gaps is necessary. When data is extremely abundant (as in the data supporting common descent), the need for data that is “new” is reduced. It is disingenuous for a creationist to insist that each proponent of common descent produce “new” data each and every time the hypothesis is reasserted. That ends up with a Zeno-type paradox. Once the “new” data is obtained, it isn’t “new” any more, and so the hypothesis of common descent is merely consistent with all known data. It may make predictions, but until those predictions are tested their outcome is unknown. Once they are tested they are merely data the hypothesis is consistent with.

    A paper that I found very useful was this:

    http://www.ncbi.nlm.nih.gov/pubmed/12133657

    I found it after I had realized that because ATP and NO levels are regulated in sync by sGC, that during sepsis when there is a very high NO level, there should also be a very high ATP. I started looking for stuff on ATP levels during sepsis and found this. In this study, they took muscle biopsies of patients in sepsis. In their abstract they didn’t mention what was to me the most interesting finding, that in the patients who survived, skeletal muscle ATP levels were higher than in normal controls. I think they didn’t mention it because it didn’t quite fit with their hypothesis of mitochondrial dysfunction and they had no explanation for it.

    I was working on my “ATP hierarchies” hypothesis at the time; that ATP concentration is a control parameter that physiology uses to modulate the activity of ATP consuming pathways. There are a zillion ATP consuming pathways, they all are regulated exquisitely well, ATP can be consumed to levels that cause necrosis by some pathways, an “optimum” organism would allocate ATP efficiently according to short and long term needs. Parsimony dictates that the ATP concentration has to be the control signal the cell uses to regulate ATP consumption (there being far more ATP consuming pathways than there are potential non-ATP signaling molecules).

    The NO regulation of ATP connects the physiology of ischemic preconditioning (where whole tissue compartments must regulate their physiological state “in sync”) produced by oxidative stress or ATP depletion with the physiology of high ATP production by mitochondria which requires a high mitochondrial potential, which generates a lot of superoxide which lowers NO levels and so disinhibits cytochrome c oxidase which allows a high flux of O2 to the mitochondria.

  26. Dr Benway says:

    It is disingenuous for a creationist to insist that each proponent of common descent produce “new” data each and every time the hypothesis is reasserted.

    Not because of the quantity of data, but because of the quantity of falsifiable challenges logged in the public record.

    The theory of evolution is covered in gold medals because it’s been subjected to countless opportunities to be proven false, yet has survived.

    There are no medals for explanations that connect the data-dots elegantly post-hoc. There is, however, the parsimony prize. Not nearly as good as a medal, but still quite nice.

  27. daedalus2u says:

    I am not interested in who has received prizes or medals or accolades. I am interested in what is the most likely correct explanation. I don’t judge the reliability of a hypothesis by whether those who thought it up have won prizes or medals.

    When comparing two explanations, which one should be preferred, the one which explains 99.99% of the data that exists but which was arrived at after the data was collected or an explanation which explains some smaller fraction of the data but which was arrived at before some of the data was collected?

    The “correct” way to approach this is via a Bayesian analysis (you should read Dr Atwood’s posts on Bayesian analysis). When that is done, the timing of the acquisition of the data becomes less important because the a priori probability is included as is data collected after the hypothesis is generated. A Bayesian analysis also allows for reliability of the data to be included. It isn’t the number of falsifiable challenges logged into the public record that matters.

    The probability of the hypotheses of evolution and common descent being correct does not depend on the timing of when those hypotheses were made and when data supporting or refuting those hypotheses was collected. I am not sure exactly what a public presentation of a hypothesis before data gathering is supposed to protect against. I suppose it could protect against post-hoc hypotheses that mindlessly fit an explanation to data. Once there is “enough” data, that become a non-starter. It doesn’t protect against conformation bias. It doesn’t protect against fraud. In most cases, the hypothesis is published with the data confirming it, i.e. a separate hypothesis is not published before the data is collected. In most cases funding agencies want some data along with the proposal. If you already have some data, does that make the hypothesis less likely?

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