Monday, March 26, 2007

Introduction to the low NO cause of ASDs

Individuals with Autism Spectrum Disorders (ASDIs) are characterized by difficulties in communication, social interaction and by repetitive behaviors. The cause(s) of ASDs remains unknown. The complex genetic disorder hypothesis posits ASDs are emergent disorders of multiple genes. In ASDs, there is a high (but not absolute) concordance between monozygous twins,[i] moderate concordance between dizygous twins,[ii] [iii] and lesser concordance between siblings. The clustering of ASDs in families, suggests genetics, but the lack of complete concordance in monozygous twins shows environmental factors are important too. The increased concordance in dizygous twins over full siblings shows that the in utero environment is important. The incidence of monoamniotic twins is quite low, perhaps insufficient for statistical information on autism rates, but monoamniotic twins can be discordant for anencephaly[iv] implying that a shared amniotic sack or placenta is not necessary or sufficient to prevent discordance in major neurological development disorders. With no generally accepted environmental cause, ASDs are thought to be primarily genetic in origin with associations of perhaps 135 genes[v]. No doubt the complex effects on brain structure and behavior observed in ASDs are not mediated via a single pathway, but calls to abandon a search for a single explanation are premature[vi]. Nitric oxide is a pleiotropic signaling molecule used in thousands of metabolic pathways where it regulates, ATP supply, O2 consumption, steroid physiology, transcription, axon targeting, epigenetic programming and many other aspects of physiology and neurodevelopment. Stress is a low NO state.[vii] I suggest that low NO in utero, brought about by maternal stress leads to the ASD phenotype in affected individuals, and the genotype that leads to the ASD phenotype was adaptive under conditions where humans evolved, in the “wild”, but is perhaps now non-adaptive due to environmental change(s). What possible advantages could the ASD phenotype hold? The most characteristic feature of ASDs is a larger brain[viii], with smaller and more numerous minicolumns.[ix]

I suggest that the diagnostic criteria for autism are the dysfunctional extreme end of the characteristic spectrum that makes humans tool making and tool using. People with less extreme ASD symptoms have Asperger’s, or can pass for “normal”, or can even be “normal” or neurologically typical individuals (NTIs). I suggest that the division between individuals who are “autistic” and “non-autistic”, is just as arbitrary as a division between individuals who are “short” and “tall”. Just as arbitrary, but vastly more complex. Being too short, or too tall, are not considered disorders, however increasing height through pharmacological (dietary supplements, growth hormone), or sartorial (high heels or lifts) mechanisms, is commonly practiced because of the adverse effect that short stature has on success in relationships with other humans. ASDs affect relationships with other humans also, and many parents of ASDIs would do “anything”, to “fix” the ASD in their child.

The ASD characteristics: difficulties in communication, social interaction and repetitive behaviors, I hypothesize are features essential during the evolution of tool making and tool using behaviors and abilities. The repetitive behavior is necessary to develop the de novo skill to manufacture stone tools. Disrupted communication is necessary to achieve sufficient social isolation, necessary for ASD individuals to ignore the “conventional wisdom” (which may be wrong) as practiced by other members of his clan or tribe. This is the essence of what Thomas Kuhn spoke of in the Structure of Scientific Revolutions[x]. To make new paradigms, one must be able to work beyond and outside of the old paradigms. This is something that “normal science” does very poorly. Peer review is good for reviewing “normal” science; it is terrible for paradigm breaking science. “Conventional wisdom” is good if the environment has remained static since the “conventional wisdom” was first adopted. Obviously a changing environment or changes in human behavior can obsolete “conventional wisdom” requiring change, otherwise we would still be living in caves, wearing skins and using stone tools, or perhaps still living in trees, or in primordial ooze. We will never know when the first ancestor(s) of humans abandoned the “conventional wisdom” of his/her group and did something new which was successful. That early human ancestor(s) did, and by doing so flourished, is beyond doubt.

[i] Kates WR, Burnette CP, Eliez S, Strunge LA, Kaplan D, Landa R, Reiss AL, Pearlson GD. Neuroanatomic Variation in Monozygotic Twin Pairs Discordant for the Narrow Phenotype for Autism. Am J Psychiatry. 2004 Mar;161(3):539-46.

[ii] Greenberg DA, Hodge SE, Sowinski J, Nicoll D. Excess of twins among affected sibling pairs with autism: implications for the etiology of autism. Am J Hum Genet. 2001 Nov;69(5):1062-7.

[iii] Visscher PM. Increased Rate of Twins among Affected Sib Pairs. Am J Hum Genet. 2002 Oct;71(4):995-6; author reply 996-9.

[iv] Lim KI, Dy C, Pugash D, Williams KP. Monoamniotic twins discordant for anencephaly managed conservatively with good outcomes: two case reports and a review of the literature. Ultrasound Obstet Gynecol. 2005 Aug;26(2):188-93.

[v] Herbert MR, Russo JP, Yang S, Roohi J, Blaxill M, Kahler SG, Cremer L, Hatchwell E. Autism and environmental genomics. Neurotoxicology 2006 Sep;27(5):671-84.

[vi] Happe F, Ronald A, Plomin R. Time to give up on a single explanation for autism. Nat Neurosci. 2006 Oct;9(10):1218-20.

[vii] Esch T, Stefano GB, Fricchione GL, Benson H. Stress-related diseases – a potential role for nitric oxide. Med Sci Monit. 2002 Jun;8(6):RA103-18.

[viii] Herbert MR. Large Brains in Autism: The Challenge of Pervasive Abnormality. Neuroscientist. 2005 Oct;11(5):417-40.

[ix] Casanova MF, Buxhoeveden DP, Switala AE, Roy E. Minicolumnar pathology in autism. Neurology. 2002 Feb 12;58(3):428-32.

[x] Thomas S. Kuhn. The Structure of Scientific Revolutions. 3d edition. University of Chicago Press, 1996.


sadunkal said...

Hi. You think your NO hypothesis may also be related to what's called the "Creutzfeldt-Jakob Disease"?

daedalus2u said...

Hi sadunkal, yes I think it is related, but not via the same mechanisms as for autism.

CJD is caused by accumulation of misfolded proteins, Typically it occurs not in the young, but in older people. I suspect the problem is due to a reduction in ATP levels due to insufficient NO. This reduces the basal level of autophagy which is what keeps protein agglomerates from accumulating. Similarly there are many proteins called heat shock proteins that keep proteins from denaturing and getting into bad conformations. Many of them are ATP powered and low ATP would be expected to decrease their regulation of proper protein conformation and an increase in misfolded proteins.

I talk about this type of thing more in later blogs, the one on the placebo effect, acute psychosis and the resolution of ASD symptoms with fever discuss reductions in ATP levels under stress.

Low ATP by any mechinsm is going to exacerbate the accumulation of damaged and misfolded proteins. Amyloidoisis is observed in things like the metabolic syndrome and not just in the CNS, but in peripheral tissues.

sadunkal said...

Ok, thanks for the fast response.

Feel free to delete this comment if it's too insignificant but I thought this book might interest you:
Explaining 'Unexplained Illnesses' by Martin Pall

The NO/ONOO- Oxidative-Inflammatory Disease Model

You probably know about this, but just in case you didn't... Actually I don't even know if it's related to your work, but I do not intend to make a research about the relation now. So delete it if it's irrelevant simply.

daedalus2u said...

I haven’t read his book, but I have read his papers discussing his hypothesis that too much nitric oxide causes the formation of peroxynitrite and this is what causes these different disorders. He is correct that peroxynitrite is involved in all of these disorders, he is incorrect that the cause is too much nitric oxide. The cause is from not enough nitric oxide.

Peroxynitrite only occurs during near stoichiometric production of NO and superoxide. With excess NO or excess superoxide peroxynitrite is not formed.

Peroxynitrite is a normal signaling molecule. The body uses it all the time. Damage only occurs when the signaling pathways get “hung up” and don’t cause a change of state quickly. In principle this could occur during the transition from a NO dominated state to a superoxide dominated state, or from a superoxide dominated state to a NO dominated state.

Switching from a NO dominated state to a superoxide dominated state is done by generating superoxide. The body has unlimited capacity to produce superoxide by many different pathways. In mitochondria, in the cytochrome P450 enzymes, in the immune system respiration burst, during hypoxia. Switching to a superoxide dominated state is a major stress response pathway. Organisms can do this very rapidly and very robustly.

Switching from a superoxide dominated state to a NO dominated state is much more difficult. There are only limited sources of NO, and most of them are used for signaling, not for bulk basal NO level regulation.

It is difficulty in switching out of the superoxide dominated state that causes excess peroxynitrite formation and peroxynitrite damage. The solution is to increase the basal NO level so the transition occurs more quickly.

What ever the NO level is, the body can always make enough superoxide to overwhelm it. This is the problem in multiple organ failure in sepsis. I talk about that in the mechanism of how mitochondria are turned off during immune system activation. That is mediated through peroxynitrite produced in the mitochondria inner matrix which turns off mitochondria. That is normally a feature, it only becomes pathological under certain quite specific and rare circumstances. I discuss that in a lot of detail.

NO and oxidative stress physiology is highly coupled and highly non-linear. It is not something that can be understood simplistically. Pall's understanding of it is wrong.

Oxidative stress is a low NO state. NO and superoxide destroy each other at near diffusion limited kinetics. It is not possible to have both simultaneously. Which ever one is in excess will destroy the other. Superoxide is the characteristic free radical of oxidative stress. Many of the adverse effects of oxidative stress are due to the lack of NO, not to the presence of superoxide.

NO is actually an excellent anti-oxidant, a few thousand times better than vitamin E.

The idea that high NO is bad is simply wrong. Nitrosative damage is not due to high NO, it is due to the combination of NO and superoxide. It is not high NO that causes mitochondrial failure during sepsis, it is superoxide in the presence of high NO. The coupled non-linear behavior of NO and superoxide cannot be looked at separately.

sadunkal said...

Ok, thanks for the detailed answer. Now this one is just out of curiosity: Did you try to contact him to warn him about his mistake? To correct him?

I ask this because I believe that this kind of communication is a necessary part of healthy science. There are too many fields where people with differing opinions reject to communicate with each other. So eventually only the more popular, powerful side is able to get its voice heard, which is not cool, especially when it comes to science...

daedalus2u said...

I completely share your sentiments that people should communicate and try to correct others' errors. I have not tried to communicate with him. There was a letter he published in Medical Hypotheses which led me to believe that he was so committed to his idea that too much NO causes all of these disorders and so committed to receiving complete credit for it, that he would be unable to appreciate his error and would attack me if I attempted to show him his error. I did communicate with someone who said he was a friend of his, asked if he could send stuff on to him, and I encouraged him to send several draft manuscripts I had written to him. I never heard back. He is touting his idea as a new medical paradigm. It isn't because it is fundamentally wrong. I think there may be a new paradigm relating to NO, but it is the opposite of what he is promoting. For him to admit his error would be for him to admit that his research direction for many years has been 180 degrees in the wrong direction. I don't dispute any of his data, only his interpretation of what it means.

I was afraid that by trying to contact him directly that I would create and enemy rather than a potential collaborator. My social skills are not great, I don't have a publication record, allies, or any kind of reputation in the field, and I was not confident of my ability to do battle in an area where he has all of those things. I don't have the capacity to sustain an attack by a powerful opponent. My view of things is shared by a few other senior researchers, but we are a distinct minority in the field. There is only a handful of us, and with grants being so "competitive", pissing off senior people in the camp of the majority is a death wish. If you lose funding, your career is over; it doesn't matter if you are right. I can be more open about my disagreements because I don't have a large lab to keep funded. I think I have greatly misjudged how difficult it would be and how long it would take to get people to adopt ideas that are obviously correct.

This is one of the adverse effects of too much "competition" in science. Ideas get funded based on the competitive and marketing skills of those pushing them, not on their scientific merit. Once your status in a field is established by a body of work, to admit error in that work is to decrease your status. To me it increases a scientist's status to be able to admit error. It makes his/her other work more reliable. The only thing that matters in the long term is reliable and correct work. The most important thing that matters in the short term is the latest fad.

There is increased nitrosative damage in all of these disorders. There is elevated nitrite, elevated nitrated proteins, elevated nitrotyrosine, and many signs of increased nitrosative damage. It is an obvious assumption that all of these signs point to too much NO. It is an obvious assumption, but it is a wrong one. The basal level of NO is ~1 nM/L (about 30 ppt by weight). This is difficult to measure in vitro, it is impossible to measure in vivo on the length (sub-cellular) and time scales (sub-second) that are important. There has been no measurement that shows lower levels of NO in any of these conditions. NO all by itself doesn't cause any nitrosative damage in vitro. It requires superoxide. This is well known.

Unless you know enough about a field, it is easy to adopt the "obvious assumptions" about it, even when they are wrong. Those obvious assumptions get fixed as the scientific paradigms that scientific peers work under and within. This is what Thomas Kuhn discusses in his book the structure of scientific revolutions. Scientific peers are very good at doing what he calls "ordinary science", that is the filling in of the details within the scientific paradigms they are working in. Scientific peers are not good at evaluating the scientific paradigms they are working in. That makes paradigm-breaking research very difficult to conceive of, to get collaborators for, to get funding to do, to get published, and to get accepted as correct. There are many paradigms that scientists are working under which are wrong. Homeostasis is one of the most egregious which I have blogged about. There are many more. Usually the best scientists in a field do appreciate that some of the major paradigms are not actually "proven", but the less senior people don't have the luxury of keeping an open mind. To get funding they need to give the appearance that they are focused on the right approach and that all other approaches are wrong. Extreme competition slows the actual rate of scientific progress by effort being wasted on competition between scientists rather than on understanding reality.

daedalus2u said...

There is another reason too. I don't like to simply point out where people are wrong. I try to focus on what is correct. There is no shortage of wrong ideas. Eventually wrong ideas will fall because they are found to be incompatible with reality. I can see the incompatibility with reality sooner for some ideas than other can. Some ideas, such as Creation are obviously incompatible with reality, but people simply can't acknowledge that. They would rather live in their delusional world.

When I say someone's ideas are wrong, I am not saying they are a bad person or stupid. They are simply wrong and have made an error either because they neglected some facts, or are misinterpreting them. I think that in science that anyone would come to the same (and correct) conclusion given enough correct data. When people come to wrong conclusions they either they haven't had enough correct data, or some of their data is wrong, or their conclusions don't follow from their premises. Pall hasn't taken into account that peroxynitrite only occurs at near stoichiometric NO and superoxide levels, and that higher NO would prevent peroxynitrite damage. The interactions of NO and superoxide are highly non-linear. He is looking in only a tiny part of their interaction space where more NO causes more peroxynitrite and assuming that is the global problem. It simply isn't.

If all I did was point out where people are wrong, I would have time for nothing else, no time to actually do something positive. I would rather do something positive. I have the ability to figure out correct ideas and articulate them in (somewhat) clear and unambiguous terms. I don't have the marketing skills to convince people that my correct ideas are correct. If people are interested in learning more about what I have to say, I would be happy to explain it to them, happy to present the chain of facts and logic that has led me to my conclusions in more detail.

In terms of how to do science, I subscribe to the Powell Doctrine of overwhelming force. One should have as much information and background in a subject as is possible. Until you have the final answer, it is not clear what information will be useful in setting you on the proper path to reach it. The final answer has to fit with every bit of reliable data that is out there, so more is always better. Sometimes sorting out what is reliable and what is not can be difficult. Data usually is reliable, conclusions often are not.

sadunkal said...

Well articulated. I understand and I agree. But in that case I have to ask you, how do you plan to get your ideas across now?

Apart from that, this might anger or disgust you, but you seem to have a lot in common with many HIV/AIDS skeptics:
Science Studies 101: Why is HIV/AIDS “science” so unreliable?

Just so you know...

sadunkal said...

Sorry, I noticed the second part just now, you partially already answer my question there. But do you think that doing your own thing will be enough to bring you success? Will you do your science and hope that some people with strong marketing skills begin to support you?

I personally think that time should be spent on changing the system fundamentally, instead of trying to adapt to its weaknesses. Both are tough jobs, but the first choice would be a longer lasting solution in my opinion...

sadunkal said...

On the other hand, making a breakthrough through defeating the system could also cause the system the change fundamentally. The breakthrough-maker can use the newly acquired powers to point to the problems within the system, then it's more likely to be paid attention to. So, I'm not sure what's really the smartest thing to do, both approaches seem to be intertwined. Eitherway, progress is crucial.

daedalus2u said...

I feel I have nothing in common with denialists of any sort. I don’t deny any reliable data. I only disagree with ideas when they don’t follow from the data. The idea of homeostasis doesn’t follow from the data about physiology. There is no data that supports the idea of homeostasis. That is because the ability to measure actual levels of parameters inside cells in vivo and non-destructively does not exist. There are no techniques to get the kind of data that would be necessary to confirm the idea of homeostasis. Pall doesn’t have any data that shows too much NO causes the problems he claims it does. The data that exists is better explained by not enough NO causing the problem, but appreciating that requires a broader, more nuanced, more complete understanding of the data and how it fits together with larger sets of data that Pall hasn’t looked at. (At least I am pretty sure he hasn’t looked at them because I feel if he did, he would come to the conclusion that the disorders are caused by low NO not by high NO.)

The only person I have control over is myself. I am not at an institution where I am in charge of others. I can’t force people to educate themselves sufficiently such that they understand that Pall’s idea is wrong, or that the idea of homeostasis is wrong.

I don’t feel that “the system” is the problem, only individuals in that system that are mistaken. I don’t think that any scientist sets out to be wrong and to put forth a wrong idea (other than true denialists and those who commit fraud).

I think the system is “wrong” only to the extent that it fosters people maintaining their mistakes and not correcting them. That isn’t a problem of “science”, it is a problem with the people doing science. In many human endeavors it doesn’t matter who is “right”, it only matters if people believe that you are right. Virtually all matters of style are completely arbitrary. There is no “right” way to style one’s hair, no right clothes to wear, no best soft drink to consume. There is only one Reality, and the scientific method is the only reliable way we know of finding out what that is.

I am not angered or disgusted by being compared to denialists. I know the comparison is not apt. I know that such a comparison is only done by people who are ignorant of the actual science behind what I am saying. If they knew the literature, they would agree with me because there is only one reasonable interpretation of that literature. I know that people who don’t know the literature can’t tell the difference between me and a denialist.

So far, no one has been able to or willing to tell me where I am wrong. If I were wrong, someone should be able to point to some data that is incompatible with my hypothesis. I have looked very hard for data incompatible with it and have been unable to find any. If someone were able to show me reliable data that falsified my various hypotheses I would abandon them or modify them until they were compatible with the new reliable data.

It is people who hold ideas that are incompatible with reliable data that are denialists. Even if they are the majority, they are still denialists.

sadunkal said...

With "the system" I wasn't talking about anything else than the people either, essentially. But this system makes it impossible to effectively use the scientific method. You said:

"I think the system is “wrong” only to the extent that it fosters people maintaining their mistakes and not correcting them. That isn’t a problem of “science”, it is a problem with the people doing science. "

Absolutely. But these "people doing science" are the way they are also as a result of some other processes. And I see these processes also as a part of the system, sort of like seeing the big picture. I mean there is a reason why not every scientist approaches science the way Feynman did. Those underlying causes need to be addressed in my opinion. I'd say these are at least problems "for science", if not "of science". This is a broad topic, it essentially contains the whole culture we're living in. The greed, the social structure, the values in society and so on... I guess your interest regarding those subjects is limited but such things directly effect you too, they effect us all. That's what I meant when I said "fundamental change". I don't know how much you really care though, sorry if this feels like a waste of time to you...

Anyway, apart from that you said things like this:

"...It is people who hold ideas that are incompatible with reliable data that are denialists. Even if they are the majority, they are still denialists..."

All you said about them in your comment were wise alright, to a limited degree. But your arguments still sound like they could source from them. Maybe this should tell you other things than what it tells you by default; maybe not about yourself, but about the others...

Hint: I'm being a little insidious here...

daedalus2u said...

You have to be more explicit than that.

Galileo was not the denialist, his persecutors were.

I do think about effects in the broader society, and many of the effects that you mention, greed, social structure, values, beliefs, why “being tough” is valued more than being compassionate is valued, are mediated to some extent by NO, and low NO makes them worse (in adults). How children develop neurologically under conditions of low NO is more complicated.

Dr Novella has a good post over at his blog today on how perception is distorted by circumstances. I posted a comment relating it to NO and why physiology is configured so that people become less rational under desperate circumstances.

I am in the process of writing some of this up, how high NO during development causes a more robust “theory of mind” and low NO causes a more robust “theory of reality”. In a nut shell, if you have a good theory of reality, you can use that theory of reality to analyze your theory of mind and avoid (to a larger extent) the types of errors that Dr Novella is talking about. If you don’t have a good theory of reality, you can’t and are trapped into thinking only with your theory of mind which isn’t very good at thinking in non-anthropomorphic terms. Since reality is fundamentally non-anthropomorphic, any good theory of reality has to be based in non-anthropomorphic terms.

That is the problem with people such as the Creationists. They don’t have the neurological structures to appreciate that what they believe based on faith is incompatible with reality. They don’t have the metacognitive ability to analyze their beliefs and trace them back to ground truth, to facts and logic. They can only trace them back to what someone told them and which they then believed.

daedalus2u said...

The only way you can tell if someone is a denialist is by testing the basis of their belief structure. You can't tell by the form without understanding the content. To attempt to do so without understanding the content is to then do what is called "cargo cult science", going through the motions and following the form, but not having the content.

sadunkal said...

Is the connection between NO and the theory of reality/mind just hypothetical or were there ever experiments conducted about things like that? I assume you have a line of logical arguments... Your language makes it sound like you found a cure for creationism, too. :)

Now to be more explicit, you said:
"Galileo was not the denialist, his persecutors were."

My point is, firstly, that his persecutors thought the opposite was true.

Secondly, assuming you're the person with the correct opinion about NO, you might find yourself in the same position against Martin Pall.

Thirdly, notice I never used the word "denialist" until this sentence. I mentioned your similarity to "HIV skeptics" and you managed to be the persecutor in this case. That was what I was trying to communicate as smoothly as I can...

Now I don't exactly know why you referred to them as "denialists", but I doubt it was NO deficiency. Nevertheless as someone who apparently knows them better than you do, I can tell you that you're not so different from them in many ways. And to be even more explicit; that's not a bad thing.

Now I don't want to distract you from your work, but if it carries enough importance for you, I'd suggest that you try to understand the HIV/AIDS skeptics better, because so far I found no rational reason to label them as "denialists". I guess I'm even one of them myself actually. The usage of the word "denialist" is only a result of lack of understanding in my opinion, at least in the case of HIV/AIDS. Sort of like you said:

"I know that such a comparison is only done by people who are ignorant of the actual science behind what I am saying. If they knew the literature, they would agree with me because there is only one reasonable interpretation of that literature."

I was saying that your words apply to the persecuted, too. Yep, I said it...

daedalus2u said...

I consider the term “HIV skeptic” to be synonymous with the term “HIV denialist”. There is such a body of literature relating infection with the HIV virus and AIDS that to deny the association is to be a denialist. When you linked to that site, I assumed you were talking about HIV denialism.

I consider HIV denialism to be worse than Creationism because it feeds into people’s wishful thinking (just like Creationism and religions in general do) and leads them to do risky things that will kill them and put other people at risk. HIV denialism does kill people. When leaders practice HIV denialism they promote useless and harmful practices.

There is a pretty good blog about retroviruses including HIV.

There is also a pretty good blog on denialism.

I just looked at one of your blogs and you are an HIV denialist. Citing the Christian Science Monitor as a reference? They deny the germ theory of disease! The only treatment they consider effective is to pray a lot. Well I am a prayer skeptic. I can’t be a prayer denialist because there is no positive data on prayer to deny.

You are still pretty young, why don’t you actually study science starting with the basics and then work your way up to the more complicated stuff. You can’t analyze the content of a debate by only looking at the form. Unless you understand science you can’t understand the content.

You notice that I haven’t talked about anyone persecuting me, or of any conspiracy against me or my ideas. I don’t think there is a conspiracy against me. I think that virtually all researchers do not understand my ideas well enough to be able to even articulate arguments against them. I have probably put 15,000 hours into reading the literature and thinking about it in the context of NO physiology and I am a very fast reader. I have read and understood thousands of papers on NO physiology. How many papers have you read and understood on HIV/AIDS? You can’t understand them unless you have the science background which you don’t have.

sadunkal said...
This comment has been removed by the author.
daedalus2u said...

You are not a skeptic, you are a cargo cult skeptic. A cargo cult skeptic is a denialist. A skeptic can only work from ground truth, from data or from logic or from their combination. You and the other HIV denialists have neither. You are trying to go through the motions of skepticism but without data or logic to back it up. You don't want "truth", you want "truthy". Something that feels true in your gut. Well, the gut is not an organ that has the capacity to evaluate data and to reason rationally. Sometimes gut feelings are correct, sometimes they are not. Conclusions based on correct facts using valid logic are always correct. I think the facts I am using are correct and the chain of logic I am using is valid. I am prepared to be found to be in error, after which I will correct which ever is wrong.

What is the premise in your blog? That by spending 15 hours looking at denialist websites a non-expert can reach conclusions that contradict the conclusions of thousands of researchers who have each spent tens of thousands of hours researching? That 15 hours at Google University is better than the millions of person hours that experts in the field have already spent? If those experts are wrong, show where they are wrong using facts and logic. No HIV denialist has done that. I am not saying this to be hurtful, but to be honest and tough. HIV denialists don't appreciate that their actions are hurting people and causing their premature deaths. That is I presume they don't appreciate it, because my presumption is that if they did appreciate their actions were killing people they would stop. That presumption may be in error.

You are only fooling yourself and other non-experts.

If you want to contradict what I have written in my blog, you have to do so using facts and logic. Attacks on me and on my methods, what I have done and what I have not done are irrelevant to the facts and logic behind my hypotheses. I know I have left out a lot of detail in what I have written. That is not because the details don't exist but because I have only a finite amount of time to put them down.

I welcome an intelligent discussion of the facts and logic behind my hypotheses. If that isn't what you are looking for, don't waste both of our times.

sadunkal said...

I had offered you to continue this through an email exchange or on my blog, because this isn't really related to this blog post anymore. But since you responded here again, I'll do the same if it's alright...

There has been a strange misunderstanding I believe. Hard to define but I'll try. You said:

"Attacks on me and on my methods, what I have done and what I have not done are irrelevant to the facts..."

You see, I never attacked you or your hypotheses. I think you perceived my pointing out your similarity with whom you choose to call "denialists" as an attack. The reason for that is that you don't truly know any "denialist". That was why I suggested you to get to know the HIV skeptics better. As far as I can see you're relying too much on the skeptics/scienceblogs community. You should consider the possibility that they may not always be right about everything, I doubt that you conducted a really independent research about the science behind HIV/AIDS. Did you? Apart from reading just what ERV or Dr. Novella had to say... Did you ever read a HIV skeptical paper from start to finish?

Try to be honest about these please, I'd like to get to know you better before I get any wrong ideas. But apart from that I'm familiar with the blogs you've sent links to; two emails I sent to Abbie were also once "featured" in ERV. That experience only increased my distrust in the mainstream scientific community, I witnessed firsthand how unscientific at least one respected HIV scientist was. What do you think about her response?

(By the way, I'm familliar with Feynman, as you'll also notice if you read the second email I sent to ERV.)

There was a little more than that actually, I invited her to correspond with the Perth Group and the last thing she said was "Get the f*ck out!" Of course such experiences didn't make it easier for me to trust her scientific thinking skills...

I was never in contact with people who run the Denialism blog, but I haven't seen them talk so much about HIV/AIDS either.

The premise of my blog is that there are unanswered questions about this HIV/AIDS issue and I'm just trying to get people to help me find answers. It's not an issue where you can safely reach a conclusion within 15 hours, but that 15 hours should get you to support more dialog between two sides, support scientific debates and attract your attention to the problems within "the system"; which also includes "ERV" and the "Denialism Blog".

I don't claim to know the answer, unlike the people who claim to know for sure that HIV causes AIDS. But from all that I read in the last 6-7 months, I got the impression that the picture is not yet complete. And I'm still looking, but I don't think that the information is already out there to complete it yet. I feel there is need for more research, and how the mainstream community approaches differing opinions is from a scientific point of view absolutely indefensible under current circumstances.

As I said, I don't think you really know the people you refer to as "denialists". I don't think you even really know what their arguments or intentions are. So all I'm saying is; before you begin throwing insults and accusations at people you don't truly know, go and meet them, talk to them, get their opinions, understand them. What makes you think that they didn't do as much reading about HIV as you did about NO for example? You can't know such details unless you understand them, just like the way you expect the other researchers to understand your ideas. How are they going to understand you if they never examine your work? Deal directly with the scientists, I'm just the messenger.

P.S. I didn't cite the Christian Science Monitor as a scientific source, just as a news source, check it out for yourself. But even so I couldn't understand what made you think that they "deny the Germ theory" ..? They didn't seem to have any problem with it as far as I could see.

daedalus2u said...

No one in HIV research says "the picture is complete."

If your age actually is 21, you can't have done as much reading on HIV as I have done on NO unless you started with a graduate degree in science when you were 13. Did you?

Unless you actually and personally understand the science, (that means understanding the logic and the facts and data behind it) you can't be a real skeptic. You can only be a follower of someone who might be or might not be a skeptic.

Since you don't know or understand the facts and logic behind the HIV debate, you can't have based your acceptance of the HIV deniers' position based on an understanding of those facts and logic.

If you don't have any facts or logic to contribute to the debate, why exactly should any scientist listen to what you have to say? Why should anyone look to you for facts or logic when you don't have any? Why should anyone think your judgment is sound when you have adopted a position that you do not understand?

When scientists who do have access to those facts and logic (such as Abbie) dismiss your opinion which is not based on facts and logic, you should not take that as a personal insult. It isn't a personal insult; it is an accurate assessment of the value of your opinion.

I only occasionally go to ERV, and haven't noticed posts or threads that you were involved in. I am not surprised that she would be insulting to an HIV denialist. That you think an insulting personal style has anything to do with scientific skills simply shows that you don't understand what science or scientific skills do involve. The HIV denialists don't have any facts or logic behind them. When that fact is pointed out, HIV denialists act as if they have been insulted. A statement of fact can't be an insult. Get some facts to support your position if you want to be taken seriously.

HIV denialists such as yourself are harmful. You wasting scientists' time refuting your bogus ideas trying to protect the naïve and gullible from your denialism; time that could be spent trying to find ways to treat and prevent HIV. You are giving cover to racists, bigots, religious zealots, homophobes and frauds who then thwart effective measures to reduce the spread of HIV. People are dying because of HIV denialists. More people will die because of your HIV denialism. It is unfortunate that you don't have the intellectual capacity to recognize your limits. This is the "arrogance of ignorance" that many ignorant people exhibit. They are so ignorant they are unable to appreciate the level of their ignorance. This is behavior that you are exhibiting.

I haven't read a great deal about HIV, probably not more than a few dozen papers. I have read enough to know that those papers fit into a coherent whole that all fits together with the rest of science that I am more familiar with. I know there are thousands of people who have read and understood hundreds or thousands of times more than I have (such as Abbie). For the most part I defer to their superior knowledge. I understand the language they use, and that what they are saying is both internally consistent and consistent with other information that is well known. The HIV denialists don't have anything like that.

Christian scientists deny the physiological basis of disease. That includes the germ theory of disease. They attribute all sickness to some kind of sin. They are denialists.

sadunkal said...

Dear Daedalus,

Look at this HIV/AIDS debate as an oppurtunity for new perspectives. Imagine how significant it would be if HIV is indeed not the cause of AIDS. Look deep inside Daedalus; don't you feel like exploring uniquely new possibilities in your life..?

One doesn't get such opputunities so often, you wouldn't really want to risk missing it... Think about it.

daedalus2u said...

Why would I waste my time on a bazillion to one shot? The chances that thousands of HIV researchers are all wrong and that I will be able to prove it and find the right answer are so small as to be non-existent.

With all this concern about energy prices and global warming, why don't you work on perpetual motion? Think of how significant it would be if you could get energy from nothing. Or turn lead into gold, or sea water into gasoline.

Just prove that what you have is real before taking other people's money or endangering other people's lives. If the HIV denialists did that, I would have less animosity toward them.

sadunkal said...

I don't know which HIV skeptics you're talking about with such disgust. Can you exactly recall what made you think about them the way you do?

Our views differ significantly there. Considering that I probably spent more time informing myself about the rethinkers, I think it's more likely that my views about them are closer to the truth than yours.

By the way, unlike the examples you gave, nobody claims to have found a way to invent something new here. The differing views are simply a result of different perception and the interpretation of the already available data. It's just a different perspective on reality, that's another reason why the label "denial" is pretty absurd, because nobody is denying anything.

And finally, I tend to believe that if you had access to the information, you wouldn't say things like "Why would I waste my time on a bazillion to one shot?". It seems that you let your prejudices prevent you from reaching the information and limit your learning.

There are also for me many things that I choose to avoid, thinking that it'll probably be just a waste of time, too unlikely and so on. But I was lucky enough to notice how complex the universe truly is and how little I'm aware of with my limited perceptual capacity. Now, although I still prioritize what I'll lend my attention to, I'm much more careful and try to ressist making up my mind for as long as possible. This allows me to dig much deeper into issues at which my former self wouldn't even have bothered to look twice, consequently I'm much more open for new knowledge. I will not claim that everything I dove into turned out to be goldworthy, but the process itself is very satisfactory. You may discover revolutionary knowledge or you may just end up making your former beliefs stronger, but either way you learn tremendous amount of new things, which reveal more unique oppurtunities in your life. To give you a very obvious example; I'll always keep your NO hypothesis in mind now. And who knows I may even dedicate my life to promote your views one day, but I would've never discovered your blog if I wasn't open enough... *

So... I sincerely hope that you'll one day take some time to approach the rethinkers in a purely objective way and spend a serious amount of time just trying to really understand(15 hours?), whwenever you think the time is right. You're not going to regret it no matter what comes out.

Perhaps, in a way, it all comes down to "The Pleasure of Finding Things Out" in the end... Or perhaps I'm just crazy...too crazy... :)

*: And if I think back I'd have never gotten to know the person who led me to visit the Neurologica blog and then click on your username to get to know you, if I wasn't a HIV skeptic in the first place. If I think back even longer all this goes back to my realization that I'll remain clueless about what's really happening in this world unless I begin to inform myself independently from all authorities. And of course before that realization there were probably things like education < family < birth < evolution < big bang < .?. and so on, but there is no need to get into all that here I guess...