Showing posts with label skepticism. Show all posts
Showing posts with label skepticism. Show all posts

Thursday, July 8, 2010

Doctor's Data sues QuackWatch

Doctor's Data sues QuackWatch

There is a story running around on the intertubes which I am blogging about just to increase the Streisand effect, not because this has much of anything to do with nitric oxide. Check out the whole scoop at the Quackometer (a site I highly recommend for the quackometer).

Doctor's Data has sued Dr Stephen Barrett of QuackWatch for a bunch of stuff, mostly for pointing out that Doctor's Data is facilitating the exploitation of parents of children with autism by participating in the bogus testing of urine for heavy metals including mercury. I happen to share Dr Stephen Barrett's opinion that this is fraudulent behavior on the part of Doctor's Data.

What reinforces my opinion that Doctor's Data is engaging in fraudulent behavior is that they object to posts by Dr Stephen Barrett that are only reports of individuals suing Doctor's Data for fraud.

I think the description of Doctor's Data use of chelation provoked urine tests for mercury by Quackwatch is accurate and does describe actual fraudulent behavior by Doctor's Data.

Unnecessary chelation is harmful, and does cause intellectual declines in experimental animals. There is zero evidence that mercury is involved in autism, much evidence that mercury is not involved in autism, no evidence that chelation helps autism symptoms. It is pure quackery.

I recommend that everyone go to Quackwatch and donate to help defeat the forces of darkness, now epitomized by Doctor's Data.

Sunday, March 14, 2010

The physiology behind xenophobia

The roots of racism, bigotry, sexism, intolerance; why people with autism are bullied so much and why some parents of autistic children have said their child would be better off dead if the autism could not be “cured”. I think this is the motivation behind the curebie mind set that some NT parents have.

This relates in part to the concept of the African philosophical term Ubuntu: being human through other humans and how lack of Ubuntu causes xenophobia. This derives from trying to understand the cognitive and communication differences in autism spectrum disorders. The concept of becoming a person through other people exactly fits with this, but in a much more literal sense than (I think) is understood in Ubuntu as a philosophical concept.

I am thinking of this not in any moral or ethical sense, rather in a purely physiological and psychological sense, how do we, as human animals, recognize and learn to recognize other entities as “human”, and how does the “human essence” that is recognized as “human” occur and develop. Considering what “essence” of someone is perceived to be “human”, and how, also leads to what happens when that “essence” is not perceived is what I think leads to the perception that someone is “non-human”, i.e. what triggers xenophobia. I am using “human” as being synonymous with “non-other” or “someone who is not so different from me that it is not OK to treat them badly”.

In other words, how do we recognize someone, something outside ourselves as something that should be treated as a fellow human being? As a brother, sister, neighbor, peer, or as an alien? As an enemy, someone who cannot be trusted and who does not deserve the normal rules of hospitality that apply to neighbors, kin and fellow human beings?

As I have been writing this it has gotten more involved and matrix-like, rather than a linear argument that is easily understood. The basic point I am trying to get across is that understanding any communication requires a Theory of Mind that matches the person you are trying to communicate with. When the two theories of mind don't match, the increased error rate triggers xenophobia via the uncanny valley effect. NT people of different races and cultures trigger xenophobia because the content of their NT ToMs doesn't match. ASDs trigger xenophobia in NTs because the fundamental structure of the ASD ToM doesn't match the NT ToM. Most of the examples I use are from politics because it is very easy to see that the xenophobia exhibited by political partisans does not have a basis in fact. The feelings of hatred come first, the arguments to support the feelings come later.

Ideas based on feelings or on facts and logic.

This feeling, that someone who is not like me belongs to a class which may be treated differently than me and my group, is a feeling, and so may be difficult or impossible to analyze rationally because at its core it is not rational. Feelings derive from physiological states, not from facts and logic. It is unreasonable to expect feelings to be rational. The feeling that one's own feelings are rational and are to believed is the essence of truthy. Stephen Colbert coined the term and discusses it saying:

Truthiness is tearing apart our country, and I don't mean the argument over who came up with the word…
It used to be, everyone was entitled to their own opinion, but not their own facts. But that's not the case anymore. Facts matter not at all. Perception is everything. It's certainty. People love the President because he's certain of his choices as a leader, even if the facts that back him up don't seem to exist. It's the fact that he's certain that is very appealing to a certain section of the country. I really feel a dichotomy in the American populace. What is important? What you want to be true, or what is true?…
Truthiness is 'What I say is right, and [nothing] anyone else says could possibly be true.' It's not only that I feel it to be true, but that I feel it to be true. There's not only an emotional quality, but there's a selfish quality.”
It is the selfishness of truthy that is its most important characteristic. It is the implicit assumption that one individual's feelings have a privileged access to truth over all other individuals. This is the essence of xenophobia, an individual's personal subjective assessment that another does not have what ever human essence it requires for that person to be a peer or equal, or even someone to not be abused or killed.
How I arrive at this is somewhat complicated. Just bear with me and try to understand the whole thing before you pick it apart. There are a lot of concepts I am trying to pull together, and putting them in a logical form isn't that easy and I have been pressed for time. I feel I need to bring up a lot of background and definitions in order for the overall concept to be understood. Not everything is in a good sequential order for easy understanding. My intent in this is not to be pejorative, but to be descriptive, to describe traits such as xenophobia as they are, so that individual bearing such traits can choose to change them (or not) as they wish. I appreciate that there is considerable stigma attached to bigotry, racism and xenophobia, and being accused of such is considered a great insult. My intent is to explain the physiology behind the feelings of xenophobia so those feelings can be understood and I hope modified or at least not acted upon. Feelings of xenophobia are morally neutral. Acting on feelings of xenophobia is not morally neutral, those actions are immoral and damaging to all involved, both the victim, the perpetrator, the enabler and the uninvolved observer.
I have an earlier version on my blog which more closely focuses on the different thinking styles on the autism spectrum. In this write-up I am trying to explain xenophobia. Why it happens, how to recognize it, how to stop it from causing problems and how to change people so they don't experience xenophobia. Getting people to not experience xenophobia is more difficult and takes their active participation in adults, not so much in children. Peer pressure can be used to compel this, but it takes active pressure and many xenophobes are in denial and resistant to change because xenophobia is such an important part of their self conceptualization. To change and become non-xenophobic means to become in part that which they now despise. This is quite important. To be non-xenophobic, one must be able to understand the other, and the only way one can understand the other is to be able to think like the other, and if one can think like the other, then one has become other-like in the most fundamental way. If one begins to understand the other before one stops hating the other, then as one's understanding increases so does one's self-hatred.
In the sense that I am using it, a Theory of Mind (ToM) produces output i.e. feelings that are direct input to another part of the ToM. The output of the ToM is “transparent”, that is there is no access to the lower hierarchical input, or the process by which the output is derived. An insulting facial expression or gesture triggers the feeling of being insulted without the conscious observation and registration that the gesture comprised a number of fingers arrayed in a particular order, or lips turned at a particular angle, and that in this particular culture that particular hand sign has a particular meaning. The gestures and body language that lead to the feelings that one is being lied to, being insulted, being put down, being loved, can't be expressed in words because the “language” that the communication is occurring in is not verbal.
I think that xenophobia is purely an outcome of a ToM and that a theory of reality (ToR) does not (and can not) lead to xenophobia. I think this is mostly because the ToM deals mostly with feelings, and those feelings are “primitives”, that the conscious brain does not have access to and good control over, and is difficult to change, and difficult to reject when they are wrong or when they don't follow from premises. In contrast a ToR is easier to change and is under much better conscious control. One adopts a ToR because it actually corresponds with reality, not because one wants to, or because one feels it is correct. In general if you have a belief and you can't derive it from facts and logic, then it is a ToM feeling, and not a ToR fact. One can have mistaken ToR “facts”, but if you refuse to change them when they are shown to be mistakes, then they are actually ToM feelings. Being able to appreciate this dichotomy is virtually impossible for someone without a good ToR.
People with a strong ToM want to be perceived to be correct because it gives them power in a human power hierarchy. They will attempt to impose their ToM on others to exert control over them. To some extent a ToM can be projected. Charismatic leaders have a strong ToM that they can use, and project and get other people to adopt. The actual truth value of the ToM is irrelevant to those using it, it is completely arbitrary. Groupthink, is an example of what can happen in an organization when ToMs are allowed to run things. The Wiki discussion points out very nicely the difficulty in problem solving in a hierarchy. When success depends in part on pleasing those higher up in the hierarchy, Groupthink is a natural consequence, which can only be avoided with substantial effort, as discussed. Groupthink lead to the serious problems of the Bay of Pigs, JFK recognized that and tried to avoid it during the Cuban Missile Crisis (fortunately he did, or we might not be here today). Drinking the Kool-Aid is another expression that means essentially the same thing. It is essentially accepting someone else's Truthy as your own.
The term Reality Based Community was originally meant as a pejorative term, applied to those who were not in political power and so had to react to the “reality” that the Neocons with political power were “creating”. Trying to create “reality” via force of will is a ToM construct.
People with a strong ToR want to be actually correct and will change their ToR when they find it to be in error. People with a strong ToM want to be perceived to be correct and want you to change your ToM to match theirs, and (in the limit) will kill you if you don't. Avoiding being killed is the ultimate reason why there is the ToM switch in Stockholm Syndrome. Threats of violence to induce adoption of a policy are virtually always ToM derived.
Truthy is a pure ToM activity, as is the postmodernism idea that everything is relative. The modernism idea of rejecting prior ideas can also be a ToM activity if another ToM is substituted for the one that is rejected. The closest things that correspond to ToR activity are Skepticism (particularly as exemplified by the James Randi Educational Foundation) and also science as exemplified by Richard Feynman. In particular see Feynman's discussion of Cargo Cult Science. I have a quote of his that exemplifies the degree of intellectual honesty that is necessary for a good ToR on my blog: “The first principle is that you must not fool yourself – and you are the easiest person to fool.” Very smart people can fool themselves. How one uses one's ability to reason is what determines the outcome. Skeptics use their intelligence to try and make their ToR correspond with actual reality by changing their ToR; Denialists use their intelligence to trick themselves into thinking reality corresponds to their ToM.
To be a good skeptic, or to have a good ToR, you can only argue from facts and then only using valid logic. If you make up your own “facts”, or use invalid arguments, you are not being a skeptic.
Denialism is a pure ToM activity. I think that some of the ideas I am expressing here are semi-consistent with the Jungian idea of the Collective Unconscious being equivalent to a shared ToM. However a ToM in the sense that I am using it is only shared within a group of humans and I don't posit any non-physical or metaphysical action at a distance to explain it or how it arises, just simple physiology. It is not “universal” in any sense. What can be universal is the overlap, the lowest common denominator of a mob for example. One does need a ToM that overlaps with social animals to understand and predict their behavior (for example dogs), and even to some extent non-social animals such as predators. Non-social animals do not really have a ToM that can be shared, so trying to understand and control them is not possible, hence the expression “herding cats”. Non-social animals do sometimes need to communicate, for example to mate, and also for predators to predict what their prey is doing, but the ToM needed for that level of communication is quite simple. It is not just that non-social animals can't be understood, the animal does not have the capacity to understand what social interaction is because it doesn't have the brain structures to instantiate that understanding.
It has been said that "Organizing autistics is like herding cats." I think this expression relates the similarities between autistics and cats as not having a robust ToM that is shared between the would-be cat (or autist) herder and the objects of their herding attempts.

Thinking requires neuroanatomy to instantiate idea.


The only way anyone can think about something is if that person has the neurological hardware to instantiate the mental concept. If the mental concept cannot be “mapped” onto the neuroanatomy of the brain, the idea cannot be held in that brain, the idea cannot be thought about. I am using “neuroanatomy” in the most general sense, a configuration of brain matter/stuff. All changes in the mind result from and are caused by changes in the physical structure of the brain (which I am calling neuroanatomy even though it may be sub-cellular in nature).

Understanding that someone without the neural hardware to instantiate the idea is unable to think about it is difficult. Most human thinking is transparent, that is it takes very little effort. It is only coming up with completely new ideas that is difficult, but like all things it always looks easy in hindsight. Bora has a good example of that kind of thinking in regarding science journalism:

You understand that it is impossible for a single person to gain a full understanding of every area of science.

- Can you play violin?
- Sure, of course
- Have you ever played?
- No. But it looks easy, I'm sure I can do it.

This is how non-scientists often think about science.”

This is how people who lack the neural hardware to understand an idea often think about the idea. They are unable to actually think about it, so they are unable to evaluate if the concept is easy or difficult. With a ToR, you know if you have or don't have a chain of logic leading from facts to what you believe is true. With a ToM, there is only the feeling, the process by which the feeling was arrived at is transparent, it is completely unknown. Sometimes the path can be figured out, that is one of the things that psychotherapy and psychoanalysis is used for. In day-to-day use, where feelings come from is mostly unknown.

Facts are independent of the neural network that instantiates them. Feelings are subjective products of the neural network that instantiates them. Feelings change due to the physiological state of the brain, facts do not. When you are tired, angry, hungry, sick, or running from a bear, feelings change and the pathways by which feelings are used to derive other feelings change. Facts do not change and the logic that connects facts does not change.

Learning is the process by which neuroanatomy remodels itself so the new neuroanatomy can instantiate the learned idea.

Being ignorant of a mental concept is equivalent to having a neuroanatomy that does not support instantiating the mental concept that one is ignorant about. The only one can become non-ignorant is to learn the concept which means modifying your neuroanatomy so the idea can be instantiated.

Learning can be looked at as modification of the brain's neural network so the new neuroanatomy can support what ever new idea it is that is being learned. This change in neuroanatomy takes a time that is dependent on how similar the new idea is to ideas that can already be instantiated.

In computers, there is a distinction made between hardware and software. There is no such distinction in natural neural networks, there is only “hardware”. I don't want to get into a mind-body argument. This is written from a completely materialistic perspective, that there are no ghosts or immaterial minds, or spirits that have influences other than through chemistry, physics and quantum mechanics. The brain is only hardware, but that hardware can change with a time constant of less than a second. That is what memory does, it records (via some unknown process) ideas in short term memory and later consolidates it into long term memory. Both of those are hardware in the sense that I am using, the sense that there are actual physical objects, cells, molecules, networks that have changed state and the “data” is recorded in that changed state, and the physics and chemistry of those physical objects determines the properties of the “memory”. It is fundamentally not like computer memory, where the type of memory does not affect the data and where “data” in the sense of software can direct the hardware to perform calculations. In brains there is only hardware, but that hardware is very complicated and can change second-to-second. A ToR in essence emulates a computer where “facts” and “logic” can be stored so they are not changed by a change in the emotional state of the organism.

Learning physics or mathematics is difficult because the normally developing neural patterning doesn't spontaneously support that type of thinking the way it supports language. Language acquisition occurs spontaneously. Essentially all infants learn to speak essentially any language that they are exposed to as infants, without an accent and with no special effort. It is not that language acquisition is easy or simple, rather that evolution has configured humans to have very powerful language acquisition systems; that either a language is spontaneously acquired, or a new language is generated de novo.

Learning is a process of neurodevelopment which must follow a path. The neuroanatomy is reconfigured a little bit at a time through neuronal remodeling to transition from the state before the mental concept can be instantiated to the neuroanatomy after the mental concept can be instantiated. Memory is a simple example, but one that requires very complex neuronal remodeling, the details of which is still not understood, yet it happens completely transparently. This is why most learning has to start with the basics, then once the basics are learned more complex ideas can be learned, and so on. The early learning configures the neuroanatomy into a state where it can be reconfigured again for later learning, and again, and again throughout the entire lifespan.

Theory of Mind: absolutely necessary for any communication

I discuss much of this in a hypothesis of autism in an earlier post.

My understanding of xenophobia and othering starts with an understanding of how people communicate, that is through a shared “theory of mind”. A “theory of mind” in this context is the cognitive hardware that converts a data stream of language into a mental concept and back. When two people communicate, the first one translates a mental concept into a data-stream of language, the data is transferred, the second person receives the data-stream through their senses, and then up converts the data-stream into a mental concept. Fundamentally, the only things that can be “communicated” are mental concepts, and those mental concepts can only be communicated if the two individuals share a common “theory of mind”, the same (or close enough) mapping of a data-stream of language onto mental concepts. What is critically important is that both individuals have neural structures that are both able to instantiate the same mental concept that they are both thinking about. If they are unable to instantiate the same mental concept, they are unable to communicate about that mental concept. All communication necessarily is a two-person activity. A failure to communicate is also a two-person activity, a failure to communicate cannot be localized to one individual.

Communication and language acquisition: the compulsion of peer pressure

Because infants are unable to speak but yet can learn to speak essentially any language as a first language with no accent, the ability to communicate in a specific language is not innate but is a product of neurodevelopment (which is innate). Usually infants will adopt the language of the majority population, usually the language of their parents.

Social animals communicate with each other. In humans the brain structures to support language and language development must be coded for genetically. Language itself must be learned or is synthesized de novo during certain periods of brain development. This point is quite important. When humans are growing up in a culture, they adopt the language of the culture, provided that the language is "well formed". If the language the adults are using is not "well formed", the children synthesize a new language that is "well formed". That is, when the children of immigrant parents grow up, they do not adopt the pidgin language their parents are speaking, they either adopt the "well formed" dominant language, or synthesize a new "well formed" Creole. The various sign languages did not become "well formed" until children grew up with signing as their first language, which they modified into a "well formed" language. This is well documented in the development of Nicaraguan sign language.

The acquisition of language in this way tells us several things; that the ability to acquire language is innate, and that there is a more "primitive" cognitive structure underlying language (by that I mean that the structure of "cognition" has a component that is hierarchically simpler than the linguistic components humans communicate with), and that neurodevelopment of language acquisition is to some extent directed by that underlying cognitive structure in ways that are transparent, i.e. not observed or noticed. Without a simpler and more primitive cognitive structure, the Creole could not be unconsciously analyzed as it is being formed to ensure the resulting Creole has a "well formed" grammar and that the specific well-formed language corresponds to what the other children are using. However, the ability to form a Creole is lost at a certain age. The immigrant parents of the Creole synthesizing children continue to speak their pidgin language. This implies that the cognitive structure that analyzes language as it is being learned and forces the develop0ing neuroanatomy to instantiate a language that is "well formed", i.e. to conform to standard default human linguistic patterns is lost (to some extent) with age. It also implies a compulsion to learn the "standard" language and a compulsion to force others to comply with the "standard".

Some individuals may not lose the ability to acquire new languages with as high fidelity as “first languages”. That ability is extremely rare and insufficiently characterized for me to discuss it further. It is not the case that the only type of “languages” that humans can understand are languages that fit the “well-formed grammar” of first languages. Pidgin languages do not fit a well-formed grammar and yet can be understood.

The development of a de novo language, such as a Creole, is a collective outcome produced by a population. It is not produced by a single individual. Another way of describing it is that the population developing the language acquires a shared neural mapping of the medium of the language (sounds, gestures, etc) to neural structures producing the mental states that are the ultimate outcome of communication (that is the ideas being communicated). In this context, there is no arbitrarily correct mapping. The mapping is correct so long as it is the mapping shared by the group. In the sense of this quote: “In any great organization it is far, far safer to be wrong with the majority than to be right alone.” (John Kenneth Galbraith); what ever the majority adopts as the linguistic mapping is the correct mapping. This is a very important point. What ever the majority adopts as correct is correct; everything else is wrong. The ability to incorporate something arbitrary into a ToM is important. It allows and is necessary to support Doublethink the holding of two contradictory ideas simultaneously while believing both of them.

For a single majority linguistic mapping to arise spontaneously there must be very powerful mechanism(s) to eliminate deviation from the mapping acquired by the majority. The majority acquire a shared Theory of Mind with respect to linguistic mapping. In other words, the differences between the shared Theory of Mind and that of any individuals in the population are reduced. The deviation is not reduced by changes to the shared theory of mind; the deviation is reduced by individuals adopting the shared ToM as their own.

This is an important point. There is no "shared" ToM. There are only individual ToMs which correspond to the shared ToM more or less. The shared TOM can only be shared to the extent that all individuals have the same components and the same structural relationships between those components. The shared ToM reflects the "lowest common denominator"; the ToM that overlaps with everyone else's ToM is all that can be shared. I think this relates to the importance of "peer pressure" in the age group capable of forming a Creole language. If peer pressure were not so compelling, a single coherent language would be difficult or even impossible to achieve.

As mentioned earlier, the parents of the generation that develops the Creole continue to speak their pidgin language. They do not participate in the Creole formation because their ToM is insufficiently plastic. Their ToM has become “fixed”.

The rigidity of an inflexible ToM maintains stability of communication over your lifetime, and of information transmitted culturally to the next generation. If your ToM doesn't support an idea, you cannot transmit it, cannot receive it, cannot understand it, or cannot even think it. When times are easy, transmitting the cultural information that led to those easy times is important. It is important to do so with high fidelity because it worked. When times are hard, the culturally transmitted information isn't working, and so needs to be abandoned or modified. The fidelity of transmission must be reduced so what ever is wrong and/or isn't working can be eliminated. I think the “hard times” skews neuronal remodeling in utero to a less social phenotype, to more toward the ASD end of the ASD spectrum. Exposure to stress in utero does increase the incidence of autism.

The “theory of mind” encompasses all communication modalities, spoken language, sign language, text, music, lip reading, gestures, and very importantly body language where emotional states are communicated. Much of the communication of emotional states is likely unconscious and we don't have conscious access to everything that is being communicated, especially when what is communicated are emotional states. What is communicated results in feelings, feelings of unease, feelings of trust, feelings of respect, feelings of every type. The details of those feelings are very important. The details of feelings produced by translation of the data stream is also a part of the ToM that is learned during early to mid childhood. This is a major mechanism by which xenophobia can be learned, peer pressure compels adoption of what the peers are doing. One has to go along to get along, even to the extent of ostracizing those that are different.

That is why being ostracized hurts. It has to be aversive or it would not be effective at enforcing a single shared ToM. Avoiding the feelings of hurt are what compel people to “go along”. It is what compels people to change their ToM, to acquire the local accent, local customs, local gestures, local ways of feeling, local ways of ostracizing those who are not “local”. I think that this is the basis for mob rule, and why as Friedrich Nietzsche said “Madness is rare in individuals - but in groups, parties, nations, and ages it is the rule.” The ToM of the mob is the lowest common denominator, the intersection of the ToM of all the individuals in the mob. The larger the mob, the smaller the intersection, and the smaller and less complex ideas can be collectively understood. I think this is why mobs tend to descend into hatred, violence and fight or flight stress responses. Those are the most primitive and universal feelings. Mobs also tend to exclude those who would provide a moderating influence.

Nietzsche also said: “The surest way to corrupt a youth is to instruct him to hold in higher esteem those who think alike than those who think differently.” I think by “corrupt” Nietzsche means “stunt the ability to think and understand”.

NT infants and children have an enormous compulsion to acquire a NT-type ToM. That compulsion is what drives the NT brain to organize itself in the NT neuroanatomy. NTs end up with communication being their “savant” ability. In ASDs, the “compulsion hardware” compels acquisition of other skills, skills that are more randomly distributed and which end up being the savant skill of that particular individual. I think this is why there is so much more diversity in ways of thinking among people with autism. ASD children have less compulsion to be the way everyone else is.

I think (but this is somewhat more speculative) that the “compulsion” module is more flexible in ASDs, and can even be “programmed” to a greater extent than in NTs. I suspect that OCD is what happens when the compulsion module gets focused on a particular and semi-dysfunctional activity. Of course, what is considered to be dysfunctional is in the mind of the beholder. To become expert in any activity, athletics, music, science, acting, writing, fighting, weaving, making stone tools, train spotting, requires extreme levels of practice. Having a compulsion to repeatedly do a task is a way to spontaneously develop expertise in that task. It takes about 10,000 hours to be come expert in a field. If you haven't spent that kind of time, you are not an expert.

ToM and pattern recognition

How communication works, is that a data stream is transferred, decoded by the ToM and matched to mental concepts via pattern recognition, either familiar mental concepts or mental concepts generated de novo. Pattern recognition is a well understood ability. All systems instantiating pattern recognition are subject to different forms of error. There is the type 1 error, the false positive, the error in wrongly identifying a false instance as positive. There is also the type 2 error, the false negative, the error in missing the correct identification of a correct instance. In a general sense any pattern recognition system can be made more sensitive, that is with a reduced type 2 error, but then there is an increased type 1 error and there are more false positives.

If there is good consilience between the “theory of mind” of the two individuals, they can communicate complex ideas in ways that are robust and nuanced. If there is not good consilience, then the communication is poor. So far I have only talked about communication and in the sense I am meaning it this communication is neutral, it has no moral or ethical component and the communication conveys no value judgment.

What triggers xenophobia

I think (and this becomes speculative now) that when two people meet, they do in effect a “Turing Test”, where they try to communicate and see if the other individual is “human enough” to trust and communicate with. I think that this hinges on whether one individual's “theory of mind” can match or emulate the “theory of mind” of the other individual and so can understand how they are thinking and can predict their responses. You are only “human enough”, if your “theory of mind” matches the “theory of mind” of the other individual. If there is insufficient consilience, then the communication error rate goes up, you fail the “Turing Test”, and xenophobia is triggered (my hypothesis) via the “uncanny valley” effect.

I see the triggering of the uncanny valley effect as being due purely to physiology and not within conscious control and so does not have a moral or ethical component. How one then responds is under conscious control (more or less) and so does have a moral and ethical component. I think this provides an explanation for a lot of human group interactions, including religions, xenophobia, bigotry and racism in all of its forms.

Michelle Dawson has a very good post about Turing and brings a modern perspective to his classic and prescient paper. Turing was gay, and experienced considerable abuse as a consequence. Abuse that ultimately led to his suicide. I think it is ironic (and very tragic) that the man who first conceived of the Turing Test in effect “failed” it as far as other humans were concerned.

I think it is the lack of consilience in the two ToMs that leads to the failing of the Turing Test and the triggering of xenophobia. It kind of has to be that way, because without consilience of the ToMs, the two individuals cannot exchange any information. They may exchange data, sounds, gestures, facial expressions, but without a ToM to translate that data into mental concepts, no information is being conveyed. What is being noticed is that there is a lack of communication going on. The error rate goes up, both type 1 and type 2 errors; getting false mental concepts that are not conveyed and missing the mental concepts that are being attempted. When those false mental concepts trigger emotions, distrust, unease, hatred, fear, distress, then fear of the other, xenophobia is happening.

I suspect that the underlying cognitive structures that enforces the development of a single Creole in children develops into the cognitive structure that does the Turing Test in adults. The compulsion of trying to communicate and behave like everyone else develops into rejecting and feeling antipathy toward everyone who doesn't behave and communicate as you do. (hypothesis)

This is where the selfishness of truthy comes in. If you privilege your own feelings above all other things, facts, logic and the feelings of others, then your mental state is unreachable. You are incapable of having a discussion because you are unable to even consider ideas different than your own.

Under this hypothesis, xenophobia comes from an inability to recognize someone as human (a type 2 error, a false negative), and derives from an inability to emulate their thinking processes and so understand their actions, motivations, and mental states. The xenophobe then substitutes (i.e. projects) what ever is convenient or what ever they are thinking (a type 1 error, a false positive) onto the person that is not understood.

Examples of xenophobia showing non-matching ToM and resulting inability to understand (mostly drawn from politics)

A classic example is when George Bush tried to explain the actions of those who flew planes into the WTC on 9/11 as “because they hate our freedoms”, which makes no sense at all. What train of logic leads from “hating freedoms” to hating people not living under a dictatorial authority to killing essentially random people in a murder-suicide? There is no train of logic. The logical explanation is that 9/11 was perpetrated to provoke a certain response, as in providing Bush with an excuse to go to war with Iraq (who played no role in 9/11) and that the expected war with Iraq would further the cause of Al Qaeda (which it abundantly did). Bin Laden played Bush perfectly, and he fell right into his trap.

In Sun Tzu's The Art of War, (III Attack by stratagem), he says:

18. Hence the saying: If you know the enemy

and know yourself, you need not fear the result of a

hundred battles. If you know yourself but not the enemy,

for every victory gained you will also suffer a defeat.

If you know neither the enemy nor yourself, you will

succumb in every battle.

Knowing the enemy” is being able to understand their thinking processes sufficiently well so as to emulate them and to be able think the way that they do. The xenophobia that George Bush exhibits is extremely dangerous in a leader, and disastrous (as observed) in a military leader.

Similarly the post 9/11 Iraq war was started with what was called “shock and awe”; with the “idea” being that individuals would be so “shocked” and “awed” that they would simply surrender. Really? What level of “shock and awe” would it take to cause Americans to simply surrender? Not surprisingly “shock and awe” didn't work. Many aspects of the initial stages of the Iraq war didn't work. They didn't work because they were produced by people completely ignorant of war and how people act when in a war, and refused to listen to people who did understand. The decision to go to war was made on the basis of Groupthink, not reasoning.

The recent Tea Party political activity in US politics can also be seen to derive from xenophobia and bigotry and not from disagreements about policy. People can disagree with President Obama and hate him for his policies, but when someone hates President Obama for policies that he does not have, the source of the hate cannot be due to his policies (because the hated policies are not his). For example when Sarah Palin hates Obama because of his “death panels” and her assertion that Obama wants to kill her son, we know that President Obama has not proposed “death panels”, and so the source of Sarah Palin's hate cannot be “death panels”, the hate must have another source. Sarah Palin's accusation of President Obama that he is proposing “death panels” is what is called a blood libel. A false accusation of heinous murder. The hating came before the blood libel because the events claimed in the blood libel never happened. The blood libel is a lie thought up to rationalize the hatred that Sarah Palin feels. The hating came first, then the blood libel, and then the blood libel can't be analyzed rationally because it “feels right” because of the hatred.

Similarly, Antisemitism and Christian hating of Jews came first, and the Antisemitic blood libel against the Jews (the lie that Jews use the blood of Christians in Passover rituals) came later. When I was about 10 years old, a Catholic boy of similar age told me that Jews used the blood of Christians in Passover rituals. I knew at the time that didn't make any sense and couldn't be true because Passover pre-dated Christianity so there could have been no Christians for Jews to use the blood of at earlier Passover ceremonies. I knew it made no sense and couldn't be true, but the boy who was telling me this believed it was true. He believed it was true because he had been told it was true. No one who told the story had ever seen it happen because it never did happen.

Similarly, left handedness has been a reason for people to be discriminated against.

In the context of bombing Iran to stop their nuclear program I have asked people who have spoken positively about bombing Iran and so stopping the Iranian nuclear program to tell me the number that would make the US surrender. Usually they respond that there is no number that would make the US surrender, not hundreds or even thousands. When asked what is different about the Iranians that one or two would cause their surrender, they are unable to reply other than by saying “but they would have to”. But in the exact same circumstances they acknowledge that US citizens would never surrender. It is the labeling of Iranians as “the other” that allows wishful thinking to project the wish of how they would act for an expectation and generate the false belief that the expectation is reasonable.

Experts in nuclear weapons find no credible reasons to expect Iran to abandon nuclear weapons following a bombing of their nuclear facilities and many reasons to expect an attack to accelerate their acquisition of them. So why is an action that cannot be expected to achieve its stated goals “on the table”? Why did presidential candidate John McCain considered bombing Iran when no credible experts on Iran, or on military activities consider that it would be successful? It is clear that John McCain is expressing that belief for a different reason, either consciously or unconsciously. That tactic by a would-be leader only works when the followers are profoundly ignorant of the group being talked about, and are willing to remain ignorant. It is a Groupthink type of reasoning.


I think this same inability to understand the other as human is involved in the gay marriage debate. Homophobic individuals are unable to conceive of gay people as fully human, and so are unable to conceive of them as having the capacity for human emotions such as love. Homophobic individuals can't imagine that a lesbian mother actually loves her child, or that her child could possibly love his/her gay mother, so the homophobe imagines that the child would be better off in foster care with an individual who might have the capacity to love and be loved.

When homophobic individuals talk about their fears of “gay culture”, what they are talking about is their fear of people being non-homophobic. One doesn't need to be gay to be non-homophobic, but many homophobic individuals are unable to appreciate that. A large part of the homophobic mind set occurs because they are attracted to same-gender individuals. They are afraid of gay culture being acceptable because it is something they can imagine themselves wanting to do. As a result, they assume everyone is like them, and the only thing keeping society from becoming the gay culture they are afraid of is the gay bashing they are doing. They are trying to enforce the Groupthink they exhibit in their narrow homophobic group.

There is an effort to repeal the “don't ask, don't tell” policy of the US military toward homosexuals. I think that eliminating xenophobia of all types in the US military is absolutely essential for them to be able to do what ever missions the civilian leaders call on them to do. As I am trying to demonstrate, xenophobia derives from an inability to understand the other. If the other cannot be understood, then the actions of the other cannot be predicted, and the other cannot be reasoned with. Diplomacy requires understanding by both sides. War, being diplomacy by other means requires it too.

Individuals of a particular group can experience xenophobia toward themselves. This is complicated and is usually tied up with abuse and the physiology behind Stockholm Syndrome. Being alive but at the bottom of a social hierarchy is better than being dead. A good description of the phenomena is tied up in a term from the history of slavery in the US, the term House Negro. A better discussion of the term is found on the blog Field Negro. Essentially the House Negro was a slave in the master's house, and had a better life with easier working conditions than the Field Negro who was a slave in the fields and was worked brutally hard. The easier life the House Negro had was built on the back of the Field Negro.

I think this is the same thinking process that lead to the taking away of children from indigenous peoples, from non-white parents by the white majority. This happened in the US, in Canada, and in Australia. I suspect that adults have somewhat higher innate connections to children, even children of different ethnicity, than they do to adults. Before those children have their own fully developed ToM, they likely are not rejected by adults. Once the ToM does develop (or does not develop so as to be consilient with the adult ToM), then xenophobia could be triggered. Removing children from their culture of origin is a way to destroy that culture. If a new generation does not grow up with that culture and language as their first language and culture, then they are lost.

In folklore, there is the mythology of changelings, the idea that a human child was stolen and a non-human child of identical appearance substituted in its place. I suspect that this is how the curbies of an earlier time rationalized the feelings they had for their autistic children. Some of them even use the metaphor of their child being stolen by autism, as if autism is an object or entity that can be anthropomorphized and then hated or blamed.

I think there are some similarities in Deaf Culture. I think the major motivation for Deaf Culture and the rejection of cochlear implants in deaf children is so that the deaf children will grow up with signing as their first language and will acquire the ToM of the Deaf Culture they grow up in. To not have a ToM that is shared by your parents is to be rejected by those parents as a changeling, and also to reject those parents. I think that deaf parents of a child who cannot sign would have feelings toward that child similar to feelings of NT parents with an autistic child. The relevant physiology is the lack of consilience between the ToMs.

I suspect that being bi-lingual with signing as one of the languages is somewhat more difficult than being multi-lingual with spoken languages because of the difficulty of making cross-connects between visual and aural senses and between hand signals and vocal muscle systems. Those difficulties are probably less than the difficulties of learning a language in the first place and likely less than the language difficulties that autistic individuals have. The communication deficits that ASDs have encompasses both language and body language, so it is likely more profound than in Deaf Culture.

As I was putting the finishing touches on this, a particularly illustrative example appeared in the news. Harry Reid, the Democratic Majority leader in the Senate, just had his wife injured in an automobile accident, where she broke her back and neck. A conservative blogger is calling on Harry Reid to “pull the plug” on her, to euthanize her. Why? Because the Right Wing Blogger can't imagine that Harry Reid has the capacity to love his wife. Love is something that only “humans” can exhibit. Since Harry Reid is a Democrat, and a liberal, he can't possibly be capable of feelings like love. It is pure projection, pure xenophobia, pure bullying. Designed (probably unconsciously) to hurt Harry Reid, those associated with Harry Reid, and to send a message to non-liberals that if you leave the Right Wing Conservative group, this will be your fate too.

There was a moment in 1954, in the Army-McCarthy hearings when Joseph McCarthy attacked a young lawyer, and Joseph Walsch said his very famous line:

Senator, may we not drop this? We know he belonged to the Lawyers Guild. Let us not assassinate this lad further, Senator. You've done enough. Have you no sense of decency, sir? At long last, have you left no sense of decency?”

In truth Joseph McCarthy didn't have a sense of decency. A sense of decency is reserved only for those one feels are fellow human beings. If someone is not felt to be a human being (because they lack a ToM that can be related to as such), then considerations normally given to fellow humans, such as decency, do not apply.

Ubuntu: the basis of humanism

I think the physiology behind the philosophy of Ubuntu is the actual root of humanism. That is the root of the physiology that makes it difficult for some people to kill other humans. In the past many soldiers were simply unable to kill other humans. Modern basic training has evolved to overcome that, the unfortunate side effect (which I think is an immutable aspect of being able to kill other humans easily) is PTSD and overt xenophobia (which has to be invoked to kill humans easily).

What counts as “human”, is the ToM that one developed as a child and young adult. That ToM is very much the human “essence” that is detected and measured by others with their own ToM. It is hard to kill others in your peer group. You recognize them with your shared ToM. To induce others to kill, you need to get their ToM to not align with the group that you want them to kill. You have to induce xenophobia via Groupthink type activities to reinforce the desired ToM that will induce xenophobia and prevent the rational thinking that a ToR does.

Being human (developing a human-recognizable ToM) occurs through interactions with other humans. You take in a bit of their ToM, and adopt it as your own. This is what Nietzsche was talking about when he said “He who fights with monsters should look to it that he himself does not become a monster. And when you gaze long into an abyss the abyss also gazes into you.” Your neuroanatomy will remodel itself to be able to do pattern recognition on what ever it is you are exposed to and then to react appropriately to it. To be able to see what is in the abyss, you need to have pattern recognition neuroanatomy that can recognize what is in the abyss, in effect you have to know what is in the abyss before you can see it.

This is why people who want to remain bigots can't have positive interactions with those they are bigoted against. To see the objects of their xenophobia as human and having human characteristics is to cause distress if they are not treated humanely. I think this is why there was such opposition to desegregation and why the GOP cannot accept diversity of opinion and have a Big Tent.

Social Hierarchies: Ubuntu and the Abrahamic Religions

As I have been thinking and writing this, I have been wanting to contrast Ubuntu with the Abrahamic religions. Not because Ubuntu is a religious principle, but because the religious principles of the Abrahamic religions have been claimed to underlie and be necessary for any sense of ethics or morality. This is not the case. The Abrahamic traditions specify a particular type of social structure, that of the top-down Kyriarchy (the Kyriarchy is analogous to the Patriarchy, but with any authority at the top). In the case of the Abrahamic religions, God is at the top, with His Prophets and priests next but above the common people who are followers, who are above non-followers.


The essence of any hierarchy is differential rights and responsibilities. Those at the top have more and those at the bottom have less. This is why power corrupts. The ToM of those at the top becomes modified so it feels as though they are better than those at the bottom, and so should have more and so they take more. More power, more money, more salary, more mates, more of everything.

In essence in Ubuntu it is 'people first'; in Abrahamic religions it is 'God first'. The “Golden rule” of 'doing unto others as you would have them do unto you', only comes after and is secondary to doing what God commands. It is like the rule in Animal Farm, all animals are equal, but some are more equal than others. All of God's children are equal, but those who follow His teachings and do whatever His representatives say to do (the self-proclaimed and self-appointed religious leaders) are more equal than those who do not. Putting God first generates a hierarchy, with those who put God first ahead of those who do not. It is a way of “othering”, a way of classifying people into people who are like us, and people who are “the other” (and so do not deserve normal human considerations) and can be enslaved or put to death at will, just as Moses said to do to non-virgin women and male children (Numbers 31:17).


The God first meme set the stage for the Divine Right of Kings, where because the first born son of the king was to be the next king, the characteristics of that king were put in place by God.

Abrahamic conflict resolution

The Abrahamic “eye for an eye” is similar. Strict punishment doesn't really deter much crime, what it does is classify individuals into criminals and non-criminals, setting up a social hierarchy with criminals at the bottom. Criminals (because they are not like us) can be subjected to maltreatment because they have been dehumanized. They are also dehumanized because they have been subjected to maltreatment. The Abrahamic eye for an eye is completely different than the Ubuntu conceptualization of justice. Justice in the Ubuntu sense is about the society getting along after the crime has happened, not about some “punishment” achieving a “balance”. It is not about a concept like “sin” being balanced by a concept of “punishment”. Justice in a Kyriarchy is about satisfying the “leader”, who will deliver “justice” after his “judgment”. It is about “justice” by fiat by the individual at the top of the hierarchy. The "Justice" is about giving you a new place in the social hierarchy. This is why "leaders" are so difficult to bring to justice. Moving them to the bottom of the hierarchy puts their followers still farther below them.

The incarceration of individuals can make crime worse because the criminals are all put together in the prison community and so the ToM of individual prisoners becomes closer to the average ToM of the prison community. Non-violent drug offenders become violent offenders. Deterrence comes not from fear of punishment (which is always contingent on being caught), but from the aversive effects of violating shared cultural norms, the same aversive effects that enforce those cultural norms in the wider community, and the same aversive effects that enforce the adoption of a shared ToM during language acquisition. When a non-violent drug offender adopts the shared ToM of the prison community (where violence is accepted), the drug offender now becomes more capable of violence.

Restitution in the Ubuntu sense is by doing something positive, by giving back to the community, by the perpetrator (and his/her family) by exhibiting Ubuntu, by doing positive things and acting in positive ways, not by having something negative happen to the perpetrator. How these two concepts work in practice is illustrated by what happen in South Africa when the Apartheid government fell (or rather what did not happen). There was no blood-bath. There was no general retribution on whites in revenge for the generations of maltreatment of blacks. In Europe following WWI, the victors extracted ruinous reparations from Germany, which set the stage for WWII.

Connection to autism, maltreatment of people on the spectrum

Autism spectrum disorders are characterized by deficiencies in abilities to communicate across all communication modalities, including body language, emotional content, nuance and the like with neurologically typical individuals, NTs In ASDs, this is caused by the lack of a ToM that matches the ToM of the NT individual. Unfortunately this activates feelings of xenophobia in NTs.

When one has feelings of xenophobia, feelings of fear, revulsion, antipathy directed toward another individual, one has the choice of how to respond. Unfortunately for NTs, the compulsion of peer pressure that causes the development of the NT ToM also compels acting on those feelings.

Problems with the standard treatment of Theory of Mind

The standard formulation of Theory of Mind, postulates that there is a “standard” way of thinking, and that people with autism are unable to mentalize in this “standard” way, and so they have a deficit in mentalizing due to their defective theory of mind. This is not correct. There is not a single or “standard” Theory of Mind, each individual has a Theory of Mind that is unique. There is no arbitrarily correct mapping of language into mental concepts. There can be no arbitrarily correct ToM. This may be very difficult for NTs to accept. Their ToM is very complex, very structured, full of nuance and with a great deal of data-compression and auto-correction that fills in the gaps in the puny data stream of language to convey mental states that are much more complex than the data stream has the data content to transmit. Two NTs can communicate very complex ideas with very little data because they have enormous amounts of data compression. The compressing and decompressing of that data is done by their ToM, and is completely transparent to them while they communicate. Much of this compression is tied up in shared cultural experiences.

Idioms convey information due to their cultural context. Phrases like the Wikipedia example “kick the bucket” have a cultural meaning that goes beyond the literal linguistic meaning. Idioms are often very difficult for people on the spectrum to appreciate. “Kick the bucket” is an idiom, but can also refer to an example of something one might do to a bucket. People on the spectrum are notorious for taking idioms literally.

How to deal with xenophobia?

This is a difficult problem with two different aspects and two possible solutions. There are the feelings that lead to xenophobia, and then there are the actions that are a result of those xenophobic feelings.

Producing individuals that do not have xenophobic feelings is most easily done in children, by exposure to individuals who are different and the prevention of the ostracizing of children who are different by adults. Mainstreaming children into regular classrooms is (I think) extremely important in accomplishing this for the next generation (of all children). It has to be done carefully, and in particular parents and teachers cannot tolerate or foster abusive behavior toward children who are different than others in the group.

A major problem is that people who have xenophobic feelings don't want to lose those feelings. They want to remain xenophobic because being a part of a community that has a common enemy does provide a sense of community and to lose the xenophobia is to lose being a part of that community. This is because excluding others is an important part of the social dynamic that produces group cohesion. We see this very clearly in homophobic communities, where even the idea of criminalizing discrimination on the basis of sexual orientation is unacceptable. There was a recent case in Virginia, where Virginia public universities had policies in place to forbid discrimination based on sexual orientation, and the Virginia Attorney General wrote them saying that such an anti-discrimination policy was forbidden.

Being in a non-xenophobic community is likely to reduce the xenophobia of the xenophobes by compelling a shift in their ToM to a less xenophobic state. It does require the non-xenophobes making known to the xenophobes that xenophobia is unacceptable. The xenophobes must be made aware that xenophobia is unacceptable but without being excluded from the non-xenophobic community.

The feelings of xenophobia engendered by a ToM are exacerbated under conditions of stress. The “fight or flight” response makes a ToR more difficult to maintain its independence of emotional state. The ToM is the more “primitive” cognitive structure, that is the default that people default back to under stress. The reason that people bully is to put their victims under stress and try and induce Stockholm Syndrome.

Monday, January 14, 2008

The Myth of Homeostasis: Implications for Neurodegeneration

Myths of physiology

This is my first attempt at a blog for the Skeptics Circle. I won't go after the obviously wrong alternate medicine cranks, quackery, woo and the delusional thinking that other skeptics handle so easily (which I see as the equivalent of fishing with dynamite in a bucket). When you are successful, the results are not entirely satisfactory because you don't end up with anything useful (just fish guts splattered everywhere). I will go after myths that are more damaging because some scientists actually believe them and waste time pursuing dead ends based on wrong ideas and clutter the literature with sloppy thinking which delays development of real treatments for real patients. I plan to write on a number of myths over time. Some may object to their favorite myths being debunked. Feel free to object and (try to) defend your myths, but be prepared to back it up with facts and logic, just as I am prepared to back up everything I say with facts and logic.

One of the most pernicious and pervasive myths, one which seriously interferes with progress in understanding and treatment of dysfunctional physiological states is the myth of homeostasis. The term was coined by Walter Bradford Cannon in 1932 from the Greek homoios (same, like, resembling) and stasis (to stand, posture). He also coined the term "fight or flight", which is actually a useful concept and is ironically completely inconsistent with the concept of homeostasis. How can physiology change to engage in fight or flight by remaining static? It can't. There has been some attempt to fix the flawed homeostasis concept with things such as "dynamic homeostasis" which I see as a simple oxymoron, and akin to the epicycles of the geocentric solar system model. Another approach is to limit the physiological parameters that homeostasis applies to, a "homeostasis of the gaps" idea. Ad hoc complications to try and rescue a failed hypothesis.

The idea of homeostasis (not a hypothesis because it is demonstrably wrong) is that in order to maintain physiologically appropriate conditions internally and maintain itself as a living organism, organisms maintain a state of homeostasis. That is many physiological parameters are maintained in a static state, and deviations from that static state are dysfunctional and are actively countered via compensatory pathways. A disease state occurs when homeostatic mechanisms are overwhelmed and homeostasis cannot be maintained. Ok, not a bad default assumption in 1932 when you are not able to really measure anything inside an organism, let alone inside an organ, or a cell or an organelle. Before there was any real idea of how cells functioned, a simplistic assumption there was something (not quite) magical called "homeostasis" that kept everything constant helped researchers to ignore the obvious complexity they couldn't begin to measure and focus on the very simple things they could measure, temperature, pH, water consumption, urine output (which usually were controlled by physiology better than the accuracy of the measurement techniques of the time). It is a step up from vitalism (which posits an imaginary life force that does the same thing), but only a small step. When all you can measure are simple things, with low precision and only on a very long time scale, everything does look constant. If you could only measure heart rate averaged over 10,000 beats (about 3 hours), you could detect a change if someone ran a marathon, you couldn't if they only ran a mile. 5 minutes with a 3x heart rate would be lost in 3 hours of 1x. Now we know that heart rate is actually chaotic, with inter-interval spacing varying in a power-law manner. Chaotic behavior is characteristic of systems of multiple coupled non-linear parameters. Many physiological systems are known to be chaotic; it is likely that virtually all of them are (all known physiological systems comprise systems of multiple coupled non-linear parameters). What about a chaotic system is or can be "static"?

On some level for an organism to maintain itself in a living state all parameters have to be kept within a certain range. But that range is not necessarily the value at rest or a constant. Organisms do remain alive with those parameters at values different than at rest. The value that physiology calls for at any moment may be different than the value at rest if a different value achieves some physiological goal different than remaining alive at rest. Are there any parameters that are kept static? Not so far as I have been able to find any evidence for in the literature. Virtually all parameters are regulated via feedback control, but that precludes stasis. Many parameters are regulated via feed-forward control. That is, parameters are adjusted in anticipation of a future need, not in response to a past need. This is a subtle point, but feed-forward is absolutely essential. When the heart pumps blood, the blood going through the heart is needed at a future time, when that blood reaches the target organ. The heart has to pump blood in anticipation of the need of the organ for that blood. When the liver puts glucose into blood, it is for a future need, when the glucose reaches the organ that uses it. Feed forward control is necessarily less precise than feedback control, but a sacrifice of efficiency for speed is a good evolutionary trade-off.

As skeptics, our default position has to be that we don't know something, rather than to assume that something has a particular property or value. Do we know that any parameters of physiology are static? No, we don't unless we actually measure them sufficiently precisely over the time and length scales in the physiological state of concern. We do know that those parameters are highly regulated, and regulated by control system(s) that are extremely complicated, extremely robust, which have evolved over billions of years, the details of which remain mostly unknown. We do know that these control systems evolved only to preserve the life and reproductive capacity of organisms that have them. There is no evolutionary pressure to maintain any physiological parameter constant; there is only evolutionary pressure to sustain the life and reproduction of the organism. If preserving the life or reproductive capacity of an organism would be better achieved by changing a control setpoint, presumably physiology would have evolved to do so (yes, I know, duh).

Some might argue that even though nothing is actually static, that homeostasis is a useful concept because it makes "intuitive sense". That is a wrong idea. The most dangerous and pernicious bad ideas are those that are wrong but which do make "intuitive sense". Most people's intuition is poorly suited to sorting out bad ideas. All woo and quackery is accepted by some because to them it makes "intuitive sense". As skeptics we must have zero tolerance for demonstrably false ideas, especially when they make intuitive sense. The problem is with our intuition. If our intuition is wrong, we must compensate for that wrong intuition and reject compelling ideas whenever they are wrong.

Researchers may not be comfortable without a backdrop of something "constant". A century ago, physics had the concept of absolute time and space. Relativity showed that concept to be wrong and reality could be better understood without it. Some physicists had great difficulty abandoning absolute time and space and adopting relativity.

Good control of any physiological parameter requires a setpoint and regulatory mechanisms to restore deviations from that setpoint. Physiological control is fabulously good. Far better than most actually appreciate. Bad control can either be good regulation around a bad setpoint, or bad regulation around a good setpoint (or some of both). Homeostasis posits that the "setpoint" is constant and fixed, and that any dysfunction is due to bad regulation about that fixed "homeostatic setpoint". A skeptical position is that any setpoint might not be fixed, it may well be a control parameter, and a deviation from the at rest setpoint might actually be a compensatory response to correct a dysfunctional state. Since we don't know every single physiological role of each and every single physiological parameter, we don't know if physiology is best served by maintaining that parameter constant or not. If that particular parameter is used as a signal (and it must be if anything is controlled by it including the parameter itself), then a deviation of that parameter may be the absolutely necessary trigger to activate a downstream pathway necessary for compensation. With a homeostatic perspective, any deviations of physiology from the "at rest" state are considered pathological or dysfunctional. But this ignores what is cause and what is effect. If physiological parameters are coupled (as we know they are), different parameters cannot be regulated independently. If multiple parameter(s) change, what is or should be the treatment goal? Which parameter(s) should be kept fixed so as to maintain homeostasis? The vast majority of physiological parameters cannot be measured and are regulated in each cell somewhat independently of all other cells. How do we choose which one(s) are important and are the "homeostatic" ones? Only through actual measurement.

I will focus on ATP concentration in cells which relates to my NO research. Don't worry, this is the only paragraph that I discuss NO in. NO regulates the ATP setpoint via sGC, and is the diffusible signal that communicates ischemic preconditioning (discussed below). Superoxide generation triggers ischemic preconditioning, consumption of NO by that superoxide turns cells generating superoxide into NO sinks, and the fall in NO propagates the ischemic preconditioning signal (as spreading long term depression in the brain) between cells. I mention it here so I can avoid mentioning NO later and confine NO physiology to this one paragraph. Some of the specifics relate to my previous blog on how fevers affect energy status in the brain and how low ATP shows up as white matter hyperintensities. I focus a lot on ATP in nerves because it is somewhat simpler there and relates to my work in autism, Alzheimer's and Amyotrophic Lateral Sclerosis (ALS). In many ways these neurodegenerative disorders are all "the same", in that they are characterized by low NO and low ATP (which I think is the ultimate cause). Just the details are different. But of course there are always a lot of details, and it is easy to get lost in those details and get caught up in the differences (which are mostly unimportant regarding treatment possibilities) and ignore the similarities (where treatment possibilities lie). The forest for the trees problem.

I will try to get into glucose regulation in a later blog. Regulation of glucose level is important under different conditions, and standard practices may be (actually are) detrimental, for example what glucose level is best to artificially impose in the ICU. Those who seek to engage in Evidence Based Medicine may want to consider the actual evidence for the optimum blood sugar under conditions such as sepsis. For example, why would we expect it to be the same as in non-sepsis when the immune system mostly functions by glycolysis and in experimental animals LPS always causes an increase in blood glucose? Maybe the hyperglycemia of sepsis is functional. I appreciate that a default of an "at rest" glucose level might be reasonable in the absence of any studies showing higher levels to be superior. But we don't know if higher levels would be superior unless we actually test them.

In the case of glucose, what glucose parameter is important? Carbohydrate consumption? Carbohydrate assimilation? Glucose level in bulk blood? Glucose level in CSF? Glucose level in extravascular fluid adjacent to the cells actually taking it up? Glucose levels inside cells? A recent (1999) "review points out that there is no compartment of glucose in the body at which all glucose is at the same concentration, and that models of glucose metabolism, including effects of insulin on glucose metabolism based on assumptions of concentration homogeneity, cannot be entirely correct." I would be more blunt; such models are wrong. (But I am not writing this for a journal requiring approval by an editor or peer reviewers who may believe in homeostasis).

In obesity, what is "homeostasis" trying to keep constant? Is it total organism energy status or energy status of the brain (the most important part of energy status)? If the part of the brain that controls appetite doesn't have enough ATP, presumably it would call for more substrate irrespective of the amount of depot fat the organism has (which the brain cannot use unless the organism is in ketosis). If there are insufficient mitochondria in the liver to support gluconeogenesis and the Cori cycle to recycle lactate into glucose, the only way to maintain glucose supply to the brain may be via consumption of carbohydrates or cachexia which may result in anorexia or obesity. Anorexia and obesity may be more similar than people think because they are both characterized by reduced energy status in the brain. You can actually have both obesity and cachexia simultaneously. During sepsis, muscle is catabolized to make glucose and body fat levels actually increase (I think to dispose of lactate but that is for a future blog).

Body temperature is pretty well controlled in humans and is often used as an example of one of the "homeostatic" parameters. Temperatures too far above or below "normal" can be fatal, but acute illness often produces a fever, and in experimental animals, blocking a temperature increase interferes with the recovery from infection. Under the homeostasis idea, preventing fever would augment homeostatic temperature control and would restore improved function more quickly. It doesn't. Raising body temperature as a response to infection is found in all vertebrates including endothermic animals such as fish. It is also found in insects.

Elevated temperatures affect how immune cells react. Presumably the body is using fever as a signaling mechanism. Driving mitochondrial respiration very high increases metabolic heat and would produce local heating, precisely the proper signal to attract macrophages and to activate them. Blocking fever may make one feel better, but it is likely to prolong the illness.

ATP Regulation

As a charged molecule, cell membranes are impermeable to ATP. Each cell necessarily regulates ATP via mechanisms which are independent of (but obviously related to) surrounding cells. Even now, there is no technique to measure ATP non-destructively in single cells on the time scale it is controlled at (sub second). Typically ATP is measured by freeze clamping a bit of tissue with liquid N2 cooled copper tongs (to stop production and consumption) and then assay it after dehydration or other denaturing of making and using enzymes. Typical minimum sample sizes are a few hundred to a few thousand cells. Measuring the averages of a few hundred cells doesn't tell very much about what ATP is doing in individual cells (or in sub-cellular compartments). ATP can be measured non-destructively by fMRI, but only in large volumes (very large compared to single cells and the length scale where ATP is actually controlled at).

ATP is exquisitely well regulated. Is there any evidence that it is kept "static"? No, there isn't. There are 3 potential ATP parameters, ATP production rate, ATP consumption rate and ATP concentration. Over the course of a day, oxidation of 2000 calories of glucose (0.56 kg) and efficient conversion to ATP produces some 55 kg of ATP. Pretty obviously the ADP and P are recycled many times and over a day's time the production and consumption is essentially exactly balanced. Since ATP isn't stored, production and consumption is balanced in essentially real time.

How many different pathways consume ATP? Conservatively it must be at least 10^5 in each cell, probably 10^6 or more. There is the synthesis of ~10^4 proteins in each cell. If we assume 10 additional pathways including post translational processing, phosphorylation, de-phosphorylation, ubiquitination, proteolysis, folding, transport by motors, and more, we can easily get to 10^5. The precise number is not necessary, simply that there are very many. Each of those pathways consumes ATP and is (to some extent) necessarily regulated separately from all others. How are all of those pathways controlled? The answer is very well.

We know that ATP consumption (and hence production) can vary by an order of magnitude (in heart muscle). We know that sufficiently severe ATP depletion causes necrotic death. We know that transient periods of acute ischemia induce what is called ischemic preconditioning (IP). Ischemic precondition is a lower ATP state, but more importantly is a lower ATP consumption state. This IP state induces a temporary state where the organism, organ, or cell can better tolerate ATP depletion and survive undamaged. The details of IP are mostly unknown, but because the effect is extremely common and robust, it no doubt represents an early evolved and fundamental stress response of cells.

Each of those 10^5 pathways can only be controlled locally. That is, the consumption of ATP is local to the molecules directly interacting with that ATP, the control of that consumption must be local too. There are many mechanisms, including phosphorylation, conformation changes, binding of peptides to block ATP consumption, many more and combinations of all of these. So what signal is used to communicate the cell's ATP status to each of those pathways and so regulate each of those pathways independently? It has to be a small molecule to be able to get every where. There are not 10^5 different small molecules, virtually all of these pathways must use the same signaling molecule for regulation appropriate to ATP status. That molecule must also couple to ATP. My conclusion is that many (if not most) pathways must use ATP itself as the signaling molecule to adjust activity to cellular ATP status. This is an extremely important conclusion. If so, it would mean that ATP cannot be regulated to be constant as the homeostasis idea requires. In addition to being the energy source, ATP must also be the signal that regulates consumption of that source. ATP would be an ideal control signal to use because it exactly tracks ATP status. No intermediate signal inducing delay or error is necessary. Regulation would be completely stable. Presumably ATP was the first signal that cells used to measure ATP status and regulate pathways accordingly. As cells evolved that signal has become more complicated, but it won't be replaced so long as it works. We know there are many proteins that bind to other proteins depending on ATP status (the heat shock proteins for example).

We know that some pathways can consume ATP until the cell dies, for example muscle contraction. A useful survival feature. The heart continues to pump until the heart kills itself from ATP depletion. One can continue to run from a bear until one drops dead from exhaustion. This demonstrates that muscle contraction has a low ATP threshold for being turned off. Other pathways such as axonal transport have higher thresholds for being turned off (see discussion below), that is they are turned off earlier as ATP levels fall.

Ischemia occurs when there is disruption of the supply of substrates (O2 and glucose) to cells. With insufficient substrate, cells cannot make ATP via their normal pathways. As ATP falls (due to insufficient substrate), cells must either make more ATP or use less (or both). Disruptions to ATP supply are leading causes of cell death. In one sense, the ability to generate sufficient ATP to maintain cellular integrity is virtually the definition of what it means to be alive. If the ability to make ATP is blocked by insufficient supply of substrates, the only way to preserve ATP concentration is to use less. With no storage, ATP not consumed is as good as new ATP generated. Following invocation of IP, cells do use less ATP, and this persists for the length of the IP period.

If IP reduces ATP consumption, can cells stay in an IP state indefinitely? It is quite clear they cannot. IP can only be a transient state, because if it was possible for cells to maintain long term a state of reduced ATP consumption, they would have evolved to do so, so that more resources could be devoted to reproduction. The IP state would become the new default metabolic state. This has not happened. We can conclude that a long term IP state is incompatible with life and/or reproduction. Since IP happens in cells that don't divide (nerves in the CNS), long term IP is incompatible with life.

Since IP reduces ATP consumption and is protective over some period of time, there must be ATP consuming pathways that are not essential during that time period and can be shut off to preserve ATP, however those pathways are essential for longer time periods (or they would not be conserved).

In my blog on acute psychosis I use the acute stressor of "running from a bear" as the archetypical stress where to be caught is virtually certain death. To escape from a bear virtually any injury short of death is an excellent trade-off. The trade-offs in IP are similar. Any injury short of death is also an excellent trade-off if it prevents death from ATP depletion. All instances of ATP depletion are either transient or the cell dies. Normally, the ATP crisis will only last until the compensatory pathways have increased ATP production to compensate. The transient nature of all ATP crises can indicate which ATP consuming pathways can be shut down. If a pathway is not crucial for life (over the length of the crisis) and is not involved in increasing ATP production (over the length of the ATP crisis) it can increase ATP availability by being shut down. This is the essence of the difference between the "fight or flight" state and the "rest and relaxation" state, the ATP status, as measured by the ATP level. This is discussed in my blog on placebos.

Let us consider nerves. Nerves only obtain ATP from oxidative phosphorylation and then only by oxidizing carbohydrates, ketone bodies and other small organic acids. They cannot obtain ATP from glycolysis or from the oxidation of lipid. Nerves are also large cells. The cell body contains the nucleus where the DNA is stored, and so is where virtually all protein synthesis occurs. The vast majority of the metabolic activity of nerves occurs in the axons, where most of the cytoplasm is. Axons are small diameter extensions of the cell that may extend for inches, or in the case of motor neurons as much as a meter from the cell body. It is down these axons that the action potential is transmitted. What is also transmitted down these axons are all the proteins and organelles synthesized in the cell body that are used at the tippy end of the axon including mitochondria. These are transported out via ATP powered motors with variable velocities, and then transported back when they get "tired". There are two modes, a slow mode (~1 micron/second), and a fast mode several times that. Usually the fast mode is for transport of endocytosed receptors on the tippy end back to the cell body. In either case, the transport time is very long compared to the duration of an ATP crisis (minutes), and this slow transport can't contribute to ATP production, so it is something that could be shut down. ATP consumption by actin is a major energy consuming pathway in neurons.

Is axonal transport shut down when there is insufficient ATP? One of the most reliable symptoms of all of the neurodegenerative diseases is what is called white matter hyperintensities (WMH). On MRI, the white matter (primarily axons so named because myelin is white, cell bodies are gray) exhibits decreased water diffusion. The precise mechanism of WMH remains unknown. I discuss some of the physiology of this in my blog on fevers and autism. Acute ischemia (from blocking a cerebral artery) causes WMH to occur very rapidly I suspect it is a controlled shut-down of axonal transport to conserve ATP. The reduced water diffusion results from reduced convective transport of water entrained by moving cargo in the axons (my hypothesis). WMH is observed to spread (spreading depression), and that spreading occurs slowly, not via action potentials.

But this blog is about homeostasis specializing in ATP homeostasis, not WMH. All of the neurodegenerative diseases characterized by WMH also are characterized by reduced metabolism, by SPECT, by fMRI, by cerebral blood flow, by MRS, by just about every measure that can be made.

What does the idea of homeostasis say about it? Not much. Homeostatic mechanisms have failed. What does a skeptic of homeostasis say about it? If a substantial fraction of ATP consumption is reduced, how many pathways are involved? 1, 10, 100's or more? For a substantial fraction to be disrupted, presumably a substantial number of the 10^5 or more pathways are disrupted. Either the regulation of hundreds of pathways has "gone bad" simultaneously and in characteristic ways for each of the diverse neurodegenerative diseases, or the regulation remains good, but around a bad setpoint. Since multiple cells are involved, and each of these pathways is regulated local to the individual cell, bad regulation of hundreds of pathways via independent mechanisms simultaneously seems extremely unlikely. That leaves good regulation around a bad setpoint. Since spreading depression can propagate and signal a cell to reduce its metabolic activity, presumably that is a normal regulatory process.

Many neurodegenerative diseases are also characterized by accumulation of damaged proteins, amyloid in Alzheimer's, Lewy bodies, tau inclusions in taupathies, alpha-synuclein in Parkinson's, polyglutamine inclusions in Huntington's, SOD1 inclusions in G93A ALS mice, and lipofuscin in all of them. Amyloid also accumulates in non-neuronal tissue in diabetes, obesity, dilative cardiomyopathy, end stage kidney failure and other degenerative diseases characterized by amyloidosis. The association of these protein inclusions is virtually universal but whether they are a cause, an effect, or merely associated with the degenerative disease is unknown. In most cases these inclusions are poly-ubiquitinated, that is they have been tagged for disposal but that disposal hasn't happened. It has been suggested that sometimes aggregation of some of these proteins may be protective. During hibernation, some animals polyphosphorylate tau, a process that is thought to precede the pathological association into aggregates observed in the taupathies. How does homeostasis explain hibernation? what is being kept static?

Cells have 3 main mechanisms for disposal of proteins that are not longer needed or that have been damaged, the proteasome and autophagy. The proteasome is used to dispose of protein molecules one at a time. They get linked to ubiquitin and then the ubiquitin-protein complex gets transported to the proteasome where first ATP powered unfoldases unfold the protein into a single length, then that piece is fed into the proteasome where ATP powered proteases break it up into little bits. The little bits are then recycled separately. The proteasome is used for control purposes also, some proteins are synthesized and then degraded and when their degradation is impeded, then they reach a level that activates something. For example Hypoxia Inducible Factor 1-alpha (HIF-1α) is rapidly synthesized and rapidly degraded under normoxia, but when the O2 tension drops, the degradation stops and HIF-1α accumulates and activates transcription.

The other two protein degradation systems are related to each other. There is Chaperone Mediated Autophagy (CMA) and autophagy. CMA can also process single proteins, autophagy is more of a bulk process where macroscopic quantities of cytoplasm are engulfed for degradation and recycle. The only way that whole organelles such as mitochondria can be recycled is via autophagy. The material to be degraded is engulfed, protease precursors are ported in, the pH is lowered via V1ATPase which pumps in protons. The low pH activates the proteases and they degrade the contents. Conditions are made reducing via porting in cysteine which reduces disulfide bonds which are exported as cystine to the cytoplasm where cysteine is regenerated. This takes ATP to produce the pH gradient. The V1ATPase is inhibited by oxidative stress, which makes sense to save ATP during IP triggered by ROS.

So what if there isn't enough ATP? Proteins that are damaged and ready to be disposed of are not doing anything constructive, they are just taking up space. All they are good for is as substrates, but they need to be taken apart and the bits remade into proteins or oxidized to make ATP. That takes time and ATP to do so. Their recycle can be put off for a little while if ATP is needed for something more important (such as running from a bear). If you have something better to do, you can always put off getting rid of the garbage. Garbage takes up less space if it is aggregated together (a trick I have found to work in living space too ;).

In conclusion (finally!), the idea of homeostasis posits that important physiological parameters are kept constant. We know that isn't the case, but many persist in clinging to that belief and invoke "homeostasis" as a principle of physiology even though there is no data to support it. It is long past time that the idea was abandoned.