Cognition and Evolution

HDAC Inhibitors and Neuropsychiatric Illness

2011-12-30T11:41:00.000-08:00

The mechanism of valproic acid (Depakote) is inhibition of histone de-acetylases. For a mood-stabilizer and anti-epileptic, this has struck many people as unexpected. A paper by Tang at Scripps in Translational Psychiatry now strengthens the link, showing the acetylation levels at some promoter regions of genes implicated in schizophrenia and bipolar disorder (samples were taken from PFC). In non-psychiatric patients the levels drop consistently with age, but in the psychiatric patients they didn't. Treatment with a novel HDAC inhibitor altered expression of the homologous genes in treated mice.

Maybe a heavy epigenetic bias to the pathophysiology of schizophrenia is the reason we've had such trouble making schizophrenia markers stick.

Novartis Bails Out of Neuroscience

2011-12-06T14:28:00.001-08:00

Novartis follows several other drugmakers' footsteps; medicinal chemist Derek Lowe provides perspective, and maybe even some optimism for small companies (i.e. San Diego biotech scene).

Blind Mathematicians Are Good At Geometry

2011-08-26T21:42:00.000-07:00

Article here.

Help Downs Syndrome Families - The Trisomy 21 Act

2011-08-09T17:53:00.000-07:00

The Trisomy 21 Act which was introduced in Congress a couple of years ago. (Down Syndrome is usually caused by having an extra copy of the twenty-first chromosome, hence the name.) Unfortunately the bill died in committee. It has been resurrected by a bipartisan team of legislators, two of whom have kids with Down Syndrome.

What will this bill do? Expand and intensify Down Syndrome programs at NIH and the CDC; create a research database; and create at least six Translational Research Centers of Excellence. Translational research is research that can go from the lab to the clinic - in other words, medicine. This is truly an exciting time to be working on Down Syndrome.

More information is available at this website. At the bottom of the page is an easy to use template to send an e-mail message to your congressperson requesting co-sponsorship of the bill. It will automatically insert your representative based on your address (just in case you don't know who it is). I completed this before I wrote this blog post.

Please share this with colleagues, friends and family members!

More information: The Trisomy 21 Act

Neuroeconomics and Delusions

2011-07-21T10:52:00.000-07:00

Previously I posted about semantic reasoning and severity of delusions. Part of the severity of delusion can be thought of as the degree to which the delusional belief affects the individual's actions. However, frequently people's non-verbal behavior seems unaffected by their delusions. Informally speaking, there would seem to be two types of delusions that do not affect behavior. The first type are not-fully-endorsed delusions, and the second are abstract, behaviorally-contentless delusions. There are insights about both that behavioral economics can offer.

The first type of less-behavior-affecting delusions (not-fully-endorsed) occurs when a delusional person has developed a coping strategy to avoid dangerous or unpleasant behavior that their delusional belief would otherwise seem to require of them, if they fully accepted its implications (this is known as not endorsing their delusion). That is, someone believes the CIA is following them and planning to harm them, but they don't attempt to move, or stop using trackable electronic communications devices, or alter their schedule. The content of the delusion could also have internally consistent components that prevent it from affecting their behavior; i.e. if they start changing their schedule, the CIA will know they know, triggering an assassination.

From the standpoint of the effect on behavior, this type of delusion would not be considered severe (again speaking informally) because although the person's social relationships may suffer, their life is not otherwise disrupted. In my previous post I stated that one way to measure the severity of the delusion would be to measure how much discomfort the individual was willing to endure to make decisions that accord with the delusion. For a not-fully-endorsed delusion, not very much. Such an approach of course would be extremely unethical and therefore not useful to consider. However, an article in Neuroscience and Biobehavioral Reviews suggests this question can be approached non-interventionally, from a neuroeconomics standpoint by looking at how suboptimal a psychotic individual's decision-making is. Less-fully-endorsed delusions would be expected to have less impact on utility maximization than more fully endorsed ones. The neuroeconomics approach is potentially a very productive one for psychiatry because it can measure utility maximization along the entire spectrum from healthy function to badly psychotic, does not get bogged down in epistemology, and most importantly, is a good proxy indicator for the overall well-being of the individual.

The second type of less-severe delusion (again, in an informal sense of the degree to which it affects behavior) is those which are behaviorally contentless; i.e., the delusion is mostly or entirely abstract and does not contain actionable content. (Whether such a belief is really a delusion is actually questionable, since an abstract belief with no external behavioral impact could be argued to be meaningless, but this is more a question for logicians or epistemologists.) These delusions cannot be endorsed, because it has no concrete implications that would make the believer behave differently. Many of these are not technically (by DSM-IV) delusions, because they are "culturally appropriate". That is, if someone believes that a statue is alive and can cry figuratively, that at a certain place someone once rode a horse into the sky, or that people are on a mission from a supernatural being to perform some act in their life, these beliefs might actually not be delusions if they are commonly held in the believers' culture. At first this exception seems an outrageous concession to political correctness, but there are salient characteristics that set "culturally-appropriate" believers apart from isolated cases. For one thing, the type of person who has decided that a statue is alive and cries figuratively - and has decided this in isolation, without meeting anyone else who believes it - is probably different from someone who believes it as a result of being brought up and repeatedly told this by trusted friends and family. Indeed, not holding or at least professing such beliefs in many cultures could be seen as irrational in the sense that failing to do so can carry a risk of ostracism or even material harm to property or person.

But what is truly interesting is that these culturally-appropriate false beliefs tend to be behaviorally-contentless, about which observation a good economic argument can be made. Culture-specific beliefs of the type described above seem to be curiously free of direct, concrete behavioral manifestations, aside from very specific rituals at certain times. The beliefs concern entities that the believer cannot define, or cannot agree upon with others who claim to hold the same beliefs (though the believer may strenuously object when told that they are unable to define their beliefs). Furthermore, the beliefs are circumscribed in the sense that their implications are not generalized to the world at large. That is, a statue-crying-believer will not generally be curious to investigate what other measurable properties of the statue might be different from a normal statue, or whether there are other crying statues with similar properties. The crying-statue believer may even find these kinds of questions offensive and actively refuse to discuss them. This behavior seems to defend a behaviorally contentless belief from being recognized as such. The question then becomes: what is the purpose of such beliefs?

One answer is that they are primarily cultural loyalty signals with no semantic content (equivalent to "Go team!" or a verbal salute), but cannot be recognized as such by the believers because then they somehow lose their function. But if that's the case, it still doesn't explain why these beliefs are behaviorally contentless. This is where a neuroeconomic argument again applies. We should expect such beliefs to tend to be behaviorally contentless because otherwise they would damage the individuals' ability to maximize utility, and they would be selected against over time. The extent to which the belief does actually affect behavior will be partly offset by the loyalty signal value, so we should expect culturally-appropriate false beliefs to correlate in terms of their contentfulness and their loyalty-signal value. That is, the more that they're useful to signal your solidarity to receive in-group benefits and avoid punishment, the more these kinds of beliefs will actually make you do things instead of just say things. At the same time, when populations with two sets of cultural beliefs come into contact, the aggregate effect of the population with more severe behavior-affecting false beliefs will become apparent, because the loyalty-signal value of the beliefs is zero between populations that do not share it.

There are clear test cases for this theory in the world today where culture-specific-false-belief areas border each other, and where there are differences in terms of utility maximization as seen in economic development. I probably don't need to point them out because several have already been written about extensively in geopolitics books.

Hasler G. Can the neuroeconomics revolution revolutionize psychiatry? Neuroscience and Biobehavioral Reviews. 2011 Apr 29. [Epub ahead of print]

The Linguistics of Bugs Bunny

2011-06-25T00:40:00.000-07:00

We can infer that Bugs Bunny's native language probably has a small phoneme inventory, so that most utterances in Bunnese would be longer than their counterparts in English (as his first statement is). I always thought this was clever and it probably is one of the things that interested me at an early age in how languages differ.

There's also a great Porky Pig cartoon where Porky insists to Daffy Duck that "buenos dias" just means "bonjour" and vice versa. The self-referentiality of this implies through comedy that something like Pinker's mentalese must exist, but I can't find the clip.

Twittering and Tweeting

2011-06-01T15:16:00.000-07:00

An early-adopter friend of mine, way back in '07 or '08, announced by Facebook that he was Twittering. At the time I hadn't heard of Twitter, and worried that he was publicly confessing he had developed an amphetamine habit. But we don't use Twitter as a verb. We tweet and re-tweet, right?

Actually, we do use Twitter as a verb - when we're speaking about
habitual use. "I'm Twittering" means "These days, I'm using Twitter" as opposed to "I'm sending a message on Twitter at the moment" - that latter sentence would be abbreviated by saying "I'm tweeting."

Many languages preserve a morphosyntactically encoded distinction between present and habitual - in fact, that's even one distinction between standard American English and the oft-villified ebonics (ebonics has it, standard Am English doesn't.) Here it's marked by requiring separate verbs. Minor observation, but interesting nonetheless.

John P. Harrington and California Native Languages

2011-05-26T11:03:00.000-07:00

John P. Harrington is known for taking copious notes on Southern California native languages. In the early twentieth century, many of these languages were already moribund. In at least one case - Tataviam, a Uto-Aztecan language spoken in the Santa Clara River basin which empties into the Pacific between Oxnard and Ventura - Harrington's notes constitute the only attestation the now-extinct language left to posterity.

It always amazes me when languages go extinct, not in isolation in the wilderness, but in the midst of booming humanity. Yes, I understand that the more numerous and economically-overbearing the new language community is (English in this case), the more likely the old language is to go extinct. But it always seems that out of all these people that settled Southern California, more than one would have been interested in recording them before they disappeared into the dust.

Button-Pushing Experiments Disprove Only One Fragile Model of Freewill

2011-03-29T09:11:00.000-07:00

Experimental evidence continues accumulating which shows that human motor behavior, and conscious awareness of the decision to perform the behavior, are often preceded by neuronal activity. This has sometimes been taken as a disproof of free will. This reasoning is flawed. If we believe "if free will exists, then it applies to all human motor behavior, and all neuronal activity engaged with this motor behavior must be conscious". Therefore, for these experiments to be a disproof, at least two assumptions must be true: 1) the entire chain of events from deciding to act to performing the act must take place within consciousness to be called free will, and 2) this simple motor task model must be generalizeable to all decision-making and motor behavior taking place on all time scales.

To #1: it is possible that the decision is made, relative to the depolarization path of the motor act, "prior" to consciousness. If this is always the case, then epiphenomenalism is the correct description of consciousness, even though we could still have free will, because we can still affect future belief states and motor acts. Consequently it's worth asking if in these models, the "originating" neuron(s) is/are really the originating neuron. Acts of apparent free will merely passing through an unconscious pathway would be even less troublesome to the idea of free will than one originating in unconscious neurons.

Analogously, we cannot choose beliefs - we don't have free will about what we perceive and believe, because perception and belief follow necessarily from sense data and from the model of the universe that exists in our brains. When we encounter sense data, we interpret it immediately as representing something and as being causally related to other things in reality. For example, you cannot see someone smile, and DECIDE consciously whether or not to believe that they are smiling, and whether or not to believe that this means something about their emotional state. But this doesn't mean that we are prisoner to those beliefs and that we cannot influence future perceptions and beliefs. If you cross-check those beliefs, you can engage in behaviors the outcomes of which can differ in obvious
ways that then will allow you to update those beliefs.

At the very least, concluding that experimental results of this sort invalidate the idea of free will, you must carry other assumptions about the nature of consciousness and free will besides just "some objects' motions cannot be predicted from prior states, and those objects have conscious experience which in some way influences those motions". The separability of these two parts of free will - the idea of unpredictable output on the one hand and input from conscious experience on the other - is important. What are the requirements for non-conscious objects with unpredictable output? Are there conscious objects with completely predictable output? Another way of asking is whether things without nervous systems can have free will.

To #2, it's worth asking whether there are classes of decisions that are more or less subject to free will; i.e., how much can we generalize these results? Certainly there are cases where free will can be an illusion, but this falls short of disproving the possibility of free will in general. By all means experimenters should continue asking this question in more settings, although a button-push model wouldn't seem to give the nervous system a chance to shine. My suspicion is that if free will exists in any action it's in long-term executive planning.

It's worth mentioning that it seems strange very strange that our own lack of free will is not obvious to us, given that prediction of the behavior of conspecifics is evolutionarily extremely important. Why the inability to do so exactly, or why the strong appearance that we are the source of action? One speculation is game-theory oriented, that the input-output chain must necessarily be clouded by introducing randomness (which wouldn't really be free will), and our sense of free will falls out of that.

Another attack on the concept is Churchland-like, and questions whether free will isn't just a bad folk idea about human behavior (which I think many enthusiasts of these experiments which agree to). It's worth asking whether belief in something like free will is universal even among non-Western humans - do Solomon Islanders and pygmies have the same belief? - and if so, what it is that predisposes humans to believing this. Do humans with a different conception of agency have different beliefs about this (Aspergers spectrum people)? Finally, do nonhuman animals also believe in free will? I encourage inventive experimentalists to think of a way to support or discredit this hypothesis. If we know different kinds of nervous systems have the same belief we can start understanding what it is we have in common with them that makes us think this.

Signing Off Until Late June

2011-01-11T17:00:00.001-08:00

As above. To study for a big test as well as maybe to get some actual original neuroscience research done. Thanks for reading, see you then. -Mike

Epistemology and Encoding Rhetorical Intention in Language

2010-12-19T18:25:00.000-08:00

Problems can arise when we misunderstand the rhetorical intentions surrounding informally stated hypotheses, which are certainly not limited to scientific endeavors. A stated hypothesis is a very strange kind of propositional utterance. When we state a hypothesis, we don't know whether it's true but we make the statement as if it were anyway - and we don't consider it to be lying or equivocating either. Why not? It has something to do with your audience knowing why you're uttering a proposition of uncertain truth value, which is exactly why if they don't know your proposition is a hypothesis, there can be problems. For example, Edward Sapir explicitly advanced the Penutian language family as a hypothesis to be investigated, and the theory was quickly adopted as gospel by the linguistic community, much to his distress. Fortunately it has largely been supported by data. It doesn't always work this way, in science or everyday conversation.

Since most languages mark questions and subjunctives explicitly, a fanciful solution would be a hypothesis particle. A simple phoneme would follow any informal statement of a hypothesis (-ba would work), and it would mean this: "I make no assertion about the truth of the proposition preceding this particle, but I want to learn the truth of this proposition, and I invite close scrutiny and criticism of this proposition in service of this goal."

But reflect further about rhetorical intention and truth value in utterances. Our classification of the rhetorical intentions is poor, since we don't recognize classes of utterances which are quite often explicitly encoded. A simple epistemological model of language is that all contentful utterances are commands, either directly to commit an action or to react to provided information, even if that's just for the listener to update his/her model of the world. As such we would expect most utterances will contain signals for rhetorical intention above and beyond the content of the sentence; there is the proposition being uttered, and the intention the utterer has of how the audience should react. Analytic philosophers attempted to approach natural language propositionally although their conclusions were sometimes provincial, hobbled as they sometimes were by an impoverished knowledge of the variety of language structures that existed outside Western Indo-European. Here is a phylogeny of coherent utterances which includes rhetorical intention.

1) COMMAND: "Get out of my house."

Extra-contential rhetorical tag: none.

1.1) Commands are the basic form of language and it is therefore not surprising that the command forms of verbs are usually morphosyntactically as, or more simple than, even the infinitive.

2) CONTENTFUL EXCLAMATION: "A blue hummingbird!"

Extra-contential rhetorical tag: "Recognize this object/event I have verbally pointed to."

2.1) Some languages (e.g. Tagalog, Washoe) do encode this intention explicitly and have focus markers which explicitly declare what the speaker wishes the listener to focus on. These markers occur throughout sentence structures and are not limited to noun-phrase exclamations like the one above.

2.2) Dependent phrase structure is always just another example of recursive phrase structure. That said, shorthand often evolves for parsimony (i.e., "There is a red book on the table" is really just shorthand for, and content-wise exactly the same as, "There is a book that is red on the table".) In languages with copulae like English, superficially there seems to be a distinction between main and dependent phrases only because of phonetic realization (or lack thereof) of recursion, but languages that lack copulae illustrate the principle more clearly.

2.3) There is also an argument that constructions like "there is" or intransitive words equivalent to "exist" are really just reflexive copulae that tie off structural loose ends. Therefore the statement above is equivalent to the proposotion "There is a hummingbird that is blue!" Potential investigation: ergative/absolutive languages with reflexive morphemes are known not to "cross systems", e.g. East Greenlandic, in which using ergative blocks use of the reflexive marker; you can only use one system at a time. So how do the reflexive copular constructions behave in ergative/absolutive languages that have both copulae and reflexivity?

3) DECLARATION: "I am going running at 3pm."

Extra-contential rhetorical tag: "I want you to accept as true the meaning of this proposition, and update your model of the world accordingly."

3.1) Although seemingly the most basic form of utterance, declarative propositions are not even close to the entirety of contentful utterances we make. Still they are zero-grade in all languages that do mark rhetorical intention.

4) YES/NO QUESTION: "Is he very tall?"

Extra-contential rhetorical tag: "I want you to reformulate this utterance as a proposition and then tell me your evaluation of its truth value."

4.1) Questions are usually marked, either by word-order changes, explicit particles (like Japanese -ka) or tone. English has few minimal pairs where tone makes a difference (e.g. permit) and such pairs are related, unlike full tone languages. Still, if the concept of minimal pairs is extended to rhetorical intention, tone is indeed explicitly encoded and certainly distinguishes minimal pairs. ("He is running for governor." "He is running for governor?" These sentences mean different things.)

4.2) Yes/no questions are therefore actually different kinds of utterances than those containing interrogative pronouns. In fact some languages do mark them differently. Latin marked verbs with the suffix -ne only in questions that did not contains interrogative pronouns.

4.3) In all cases that I know of, the verb dominates other parts of speech in taking on question particle - that is, if there's a verb in a sentence and a language has a question particle, the particle attaches to the verb. (Case in point, in Japanese, -ka typically goes on the verb but if a single-noun utterance requesting clarification, the question particle can go on the noun; "He's working in the city," one speaker says, and the other says "Takamatsu-ka,", i.e. "In Takamatsu?"

I have argued previously that verbs and adjectives are both first-order modifiers, but that some first-order modifiers can modify two nouns simultaneously (these are called transitive verbs.) In this view, nouns alone cannot create a proposition since there is no relationship stated between them without verbs. Therefore, it makes sense that the rhetorical marker would be placed on the verb that changes the utterance from a list into a proposition.

5) INTERROGATIVE-PRONOUN-CONTAINING QUESTION: "What is the best restaurant in Portland?"

Extra-contential rhetorical tag: "This is a proposition whose truth value cannot be evaluated since I have deliberately used a placeholder ('what'). I want listeners to reformulate the statement as a proposition but include information that can be plugged into the placeholder slot in such a way as to make the proposition true."

5.1) Interrogative-pronoun containing questions are also usually marked in some way (by word-order, tone, and/or explicit morphemes.)

5.2) Languages often have multiple interrogative pronouns for different types of nominal information, but never to my knowledge are there dedicated adjectival, verbal, or other interrogative words. Interrogative pronouns can be pressed into service for one-off service as verbs and even productively undergo morphosyntactic operations: (Imagine a woman has just been told her twelve year-old son was seen driving to school. "He was what-ing to school?" Nonetheless these kinds of operations on interrogative pronouns are never formalized.)

6) CONTINGENT DECLARATION: "If it rains today, you're on your own."

Extra-contential rhetorical tag: "I have explicitly marked off a proposition whose truth value is influenced by other propositions stated in close proximity and whose truth I may not be certain of, or by the way I obtained the information."

6.1) There are two sub-structures here: one is the typical if-then statement formulation for subordinate clauses we normally think of, but there is also the case of evidential markers most famous among Tupi-Guarani languages. Both systems are ways of explicitly marking the truth-weighting that the listener should give to the proposition so marked.

Though it doesn't merit a separate entry here, it's interesting that hypotheses aren't exactly questions, but they aren't exactly subordinate clauses either (though a hypothesis can be stated as both.) It's my suspicion that humans not engaged in research do not engage in extended hypotheticals - the propositions they are unsure about tend to be simple enough that their hypotheses are all contained in single clauses delineated by if-then markers. For most humans, thoughts complicated enough to require more than one sentence and which are of uncertain truth are merely deception, not hypotheses to be tested.

However if English does follow my humorous suggestion to develop an explicit hypothesis particle and a seventh utterance category, then I should re-state my earlier sentence as "A simple epistemological model of language is that all contentful utterances are commands, either directly to commit an action or to react to provided information, even if that's just for the listener to update his/her model of the world-ba."

The Verb Regularization Rate in English

2010-12-19T10:21:00.000-08:00

"The half-life of an irregular verb scales as the square root of its usage frequency: a verb that is 100 times less frequent regularizes 10 times as fast." From Lieberman et al in Nature. An interesting question is to what other morphosyntactic rules this generalizes to, like noun plurals (and to what extent is it influenced by phonetic realization. My guess: not very much.) Pinker and many others knew qualitatively that the less a verb is used, the more likely it is to become regular in a given time period. Now we have the quantitative rule.

Gene Ancestry Visualization Tool?

2010-09-20T19:55:00.000-07:00

Most people are familiar with the radial-wheel format of showing the descent of species, like this one:

Image credit Bristol University Department of Chemistry

What would be really cool, and may already exist, which is why I'm posting this, is the same tool existed, except for gene ancestry. (And here is where I make obvious my ignorance of bioinformatics and the descent of genes both.) Genes can often be shown to originate by duplication events. I'm probably being naive about the extent to which the ancestry of genes results from similar events, or can be traced back to common ancestors shared with other genes in the same genome. But unless there was a lateral transfer event, genes all have to have common ancestry with other sequences in the organism, correct?

Ultimately we'd see another radial circle, except with genes radiating out from a common ancestor. The outer surface would be the human genome as it is now. You could place nested concentric circles representing previous phases of the genome (see mock-up below). Yes, I know the "surface" separating primates from non-primates (for example) doesn't represent any qualitative break, and the circle would be pretty lumpy since not all genes or gene families would branch and mutate at the same rates. (Genes I picked are illustrative only.)

Now, there are lots more genes than you could legibly read on a computer-screen-sized wheel, but this is also true for the species-descent wheel, which uses representative organisms. In my dream app, you could select certain gene families or genes with products that catalyzed certain classes or reactions or interacted with other gene products. The point of such a visualization is that you could more easily see when pathways started appearing or becoming more complex. Of course there will have been lots of genes lost in the interim, so we couldn't get a complete picture of what the genome was like at each point in the past. (Going back to the Grand-Daddy autocatalytic RNA would be cool, but unlikely.) If the gene-product features are sufficiently advanced you could even conceivably find "holes" in pathways at ancestral stages where the must have been gene products whose genes are no longer in the genome.

If there are any tools similar to this already out there, I would greatly appreciate a comment. This would be a valuable tool to investigate the evolution of pathways and systems. Especially neurons, of course.

Lewy Body Dementia and Alpha Synuclein as a Lipid Manipulator

2010-09-19T17:37:00.000-07:00

In terms of understanding moment-to-moment awareness, cognitive hypofunction disorders with clear genetic contributions are often uninteresting. That is, the problem is usually that the wiring isn't there, or is wrong. The reason this is uninteresting is that if you're interested in what underlies moment-to-moment consciousness, you have to look for properties of the brain that change on the same time-scale, allowing our subjective awareness to represent some of the information in the outside world.

For this reason, pharmacology often presents more research opportunities than disease states, in particular NMDA antagonists and HT2A agonists. But there is a disease state which is notorious for hour-to-hour (or more) fluctuations in cognitive status, dementia with Lewy bodies. As you can see from the linked reference, it's not yet clear whether the disease is a sub-type of Alzheimers, or a distinct condition.

Lewy bodies are alpha-synuclein plus ubiquitin inclusions that appear in neurons specific parts of the brain in disease states; the ubiquitin suggests that these are clumps of protein the neuron is trying to degrade. Their presence is not necessarily indicative that the patient had any of the additional symptoms of Lewy body dementia. Clinical Lewy body dementia is associated with symptoms above and beyond what Alzheimers patients suffer. It also has significant overlap with Parkinson's; specifically, patients exhibit both the motor decline of PD as well as REM sleep disorder. Unlike Alzheimers, onset is not insidious. Unlike either Alzheimers or PD patients and most relevant here, Lewy body dementia patients usually have recurrent visual hallucinations, and are extremely sensitive to dopaminergic- and cholinergic-modifying medications.

When we think of real-time changes to nervous systems, we usually think of information being transmitted in an electrochemically-mediated way by neurotransmitter vesicle diffusion and membrane depolarization. Membrane potentials would also be dramatically and rapidly effected by changes in lipid membrane properties, so I had considered previously whether there were proteins expressed in brain that manipulated or maintained membrane lipid contents. It's interesting that alpha synuclein a) is known to be located on the cell membrane in some fraction, b) is natively unfolded in the cytosol, c) interacts with polyunsaturated fatty acids, d) interacts with membranes correlating with serine phosphyorylation and e) still hasn't been assigned a clear function.

This is why a recent Journal of Molecular Neuroscience paper by Riedel et al at the University of Oldenburg is important. Using an oligodendroglial cell line, they demonstrated the creation of a-synuclein aggregates (in vitro Lewy bodies) both in cells that had a point mutation in a-synuclein predisposing them to aggregate formation, as well as in wild-type cells. This was done by adding DHA (by the way, an omega 3 polyunsaturated fatty acid) and then hydrogen peroxide for oxidative stress. Alpha synuclein aggregates formed both in the mutant cell line as well as in the wild type, though the mutant cells' aggregates were bigger (all compared to non-treated controls).

My hypothesis is that alpha-synuclein is responsible for lipid processing of neuronal membranes to maintain electrochemical constancy, in response to physiologically rapid (minutes to hours) changes in the environment of the cell. In addition to the specific deficits in Lewy body dementia (associated with the brain region where the Lewy bodies appear), this may also explain the rapid fluctuation in cognitive status - cell membranes are unable to respond to a changing electrochemical environment because there's a problem with the protein that controls their lipid content. When alpha-synuclein catches up or the triggering physiological change (pH, solute concentration) reverses to previous levels, the cognitive deficits may disappear.

These findings, though they show an interaction, are therefore causally backwards - here, changes to lipids are initiating aggregation. It could be that once aggregation begins, alpha-synuclein function is off-line, and any new alpha-synuclein produced by the cell gets immediately caught in the tangle and can't perform. (There's evidence that there's more than normal at the membrane in disease states.) Here are future experiments, which in my quick survey of the literature I may have missed: 1) patch clamp recordings of dopamine receptors on cells in culture with loss-of-function mutations or knockouts of alpha synuclein, especially in response to differences in charge, pH, and buffer concentration (to mimic physiologic changes in extracellular fluid). 2) Measurement of individual fatty acid chains in knockout relative to control, in terms of their incorporation into cell membranes.

I'm both excited and nervous because in the coming weeks I will be interacting with patients in the clinic who have this disease, which is why I'm motivated to understand it.

Thoughts on Newcomb

2010-08-21T10:10:00.000-07:00

I'm currently reading Robert Nozick's Socratic Puzzles. It contains two essays about Newcomb's Problem. If you've not encountered Newcomb before, a brief description follows, and if you want more, the most discussion I've seen anywhere is at Less Wrong. I can sum up this post thusly: how can Newcomb be a hard problem?

Imagine a superintelligent being (a god, or an alien grad student as Nozick imagines, or more plausibly a UCSD medical student. It's up to you.) This superintelligent being says that it can predict your actions perfectly. It shows you two boxes, Box #1 and Box #2, into which it will place money according to rules that I will shortly give. As for you, you have two options: either open both boxes and take the money from both if there is any, or open only Box #2 and take the money from just Box #2. Now here are the rules, and the kicker. Since the being can predict your actions perfectly, it does the following trick. If it predicts that you're going to take just Box #2, it will place a thousand dollars in box #1, and a million dollars in Box #2. So in this instance, you will get a million dollars, but you'll miss out on the thousand in box #1. On the other hand, if it predicts that you will take both boxes, the being will place a thousand dollars in box #1, but place nothing in Box #2. In that case, you end up with just a thousand dollars. So in other words: the being always puts a thousand dollars in Box #1, whereas in Box #2 there's either a million, or nothing.

So, now the superintelligent being has gone back to its home planet of La Jolla, and you are left wondering what to do. Assuming you want the most money possible, which option do you pick and why?

Figure 1. Decision table for Newcomb's Problem.

There's been a lot of discussion about Newcomb's Box, and not all of the responses adhere to the standard one-or-both answer. But I take the point of this particular logic-koan to be that we're to decide based on the givens of the problem which of the options we would take, so cute answers about trying to cheat, making side bets, etc. are wasting our time. If we're going to introduce those kinds of non-systematic "real world" options into this exercise, then we're going to need a lot more context than we currently have to make a decision. In fact after ten years living in Berkeley I'm surprised that I haven't yet met someone on a street corner claiming to be an alien with a million dollars for me, but if I did I would walk away and not play at all. (Come to think of it, I frequently get similar spontaneous offers of a million dollars or more in my spam folder which I ignore at my peril.)

My own answer is to take only box #2, expecting to get a million dollars. Why? Because I want a million dollars, and the superintelligent alien is apparently smart enough to know that I'll gladly cooperate and not try to make myself unpredictable (more on this in a moment). Why try to be a smart-ass about it? (It's both to your disadvantage and not even possible anyway per the terms of the problem.) The being told you where it would put the million dollars (or not) based on your actions, and it's a given in the problem that the being is perfect at predicting your actions. This is what gives the both-boxers fits. They say one-boxers are idiots because if the being got my choice wrong, it didn't put anything in box #2 because it thought I would choose both. If the being is wrong, I open only box #2, and I get zero (because the alien thought I was going to take both and least get a grand, but he was having an off day.)

I will be beating the following dead horse a lot here: the problem states you have a reliable predictor. Why does Figure 1 above even have a right-side column? If you assume the being is fallible then you're not thinking about Newcomb's problem as stated any more: you're ascribing properties to the being that either conflict with what is given in the problem, or your're making stuff up. (Maybe the alien is fallible and copper and zinc are toxic to it! That way it won't predict in time that I'm going to kill it by throwing my spare pennies and brass keys at it, and then I can get the full amount from both boxes! Sucker. Ridiculous? No more than worrying about the given perfect predictor's not being perfect.)

Figure 2. Correction to Figure 1. This figure is the actual real table for Newcomb's Problem. Figure 1 is somebody else-not-Newcomb's problem that features fallible aliens.

Complaints about the logic of the Box #2-only response (which is the majority's response, if the ones Nozick cites in one of his essays are representative) typically focus on two things. One, that we're assuming reverse causality, that we must think our choice of the boxes will make there be a million dollars in it; and two, that it suggests we don't have free will. I dismiss the second objection out of hand because the whole point of the problem is that the being is a reliable predictor of human behavior - for that one aspect of your behavior, in this problem, no, you don't have free will. Look: we already accepted a being with near-perfect predictive powers. Without that, then the problem changes and we have to guess how likely the being is to get it right. But as long as we have Mr./Ms. Perfect Predictor, then the nature or mechanism is unimportant. You can justify how it accomplishes this however you like (we don't have free will in this respect, or the alien can travel through time) but the point is, any cleverness or strategy or philosophizing you do has already been taken into account by the alien.

But things can be predicted in our world, including human behavior, and for some reason this doesn't seem to evince outcries about undermining the concept of free will. Like it or not, other humans predict things about you all the time that you think you'd have some conscious control over - whether you'll quit smoking, your credit score, your mortality - and across the population, these predictions are quite robust. They don't always have the individual exactitude that our alien friend does of course. But at the very least you must concede that if our alien friend is even as smart as humans, after playing this game multiple times with us, its ability to predict which box you take would be greater than random chance, and you would get some information about which box you should pick based on this. Being completely honest, I think a lot of the resistance to two-boxing comes from the repugnance with which some people regard the idea that their behavior is extremely predictable. (Hey! News flash: it is.) Nozick even offers additional information in his example by saying that you've seen friends and colleagues play the same game, and the being predicted their choice reliably each time. Come on Plato, do you want a million dollars or not? Absolute no-brainer!

The first objection (regarding self-referential decision-making) is slightly more fertile ground for argument and it's the one to which Nozick devotes the most time. The idea is that you're engaging in circular logic: I'm deciding to one-box, therefore the being knew I would one-box, therefore I should decide to one-box. (Again: what's the whole point of the exercise? That whatever decision you're about to make, the being knew you would do it, including all the mental gyrations you're going through to get to your answer.) Nozick gives the example of a person who doesn't know whether his father is Person A or Person B. Person A was a university scientist and died of a painful disease in mid-life which would certainly be passed onto all offspring; children of person A would be expected to display certain aptitude for technical subject. Person B was an athlete, and likewise his children would be expected to display an athletic character. So the troubled young man is deciding on a career, noting that he has excelled equally in both baseball and engineering. "I certainly wouldn't want to have a painful genetic disease. Therefore, I'll choose a career in baseball. Since I've chosen a career in baseball, that means my true prowess is in athletics and therefore, B was my father, and I won't get a genetic disease. Phew!"

Yes, that would be a ridiculous decision process. The difference between the two is this: the category the decider is in the whole time is defined in Newcomb as definitely affecting the decision, whereas in Nozick's parallel, it does not (he could've gone either way.) Whatever you decide in Newcomb, the alien knew you would go through your whole sequence of contortions, and you were in that category all the while. Whether such a deterministic category is meaningful is a different and probably more interesting question than Newcomb as-is. Here's another example: you're in a national park, following a marked trail. You get so far along the trail until you come to a frighteningly steep rock face with only a single cable hammered into it. You reason, "I am about to proceed up these cables. If I'm about to do it, it's only because my action was anticipated by the national park people who design the map and trails and they can predict my actions as a reasonably fit and sensible hiker, and furthermore they put these cables here; they're not in the business of encouraging people to do foolishly dangerous things. Therefore, because I am going to do it, it is safe and I should do it." (Any reader who's ever braved the cables on Half Dome in Yosemite by him or herself without knowing ahead of time what they were getting into has had this exact experience.) This replicates the decision process relating to the for-some-reason mysterious perfect predictor: "I am about to open Box #2 only. If I'm about to open it, the superintelligent being would have put a million dollars in it. Therefore I should open Box #2 only." In fact, all the time we go through such circular reasoning processes as they relate to other human beings who are predicting are actions either in general or specifically for us: I am going to do A, and A wouldn't be available unless other agents who can predict my actions reasonably well knew I would come along and do A, therefore I should do A." This still may be an epistemological mess (something I'm not going to debate here) but the fact is that we use this kind of reasoning constantly, living in a world shaped in the to-us most salient ways by other agents who can predict our actions. I used the example of the national park because that we use that kind of reasoning becomes obvious when you're trying to decide whether to climb something or undertake an otherwise risky proposition in a wilderness area, away from any trails or markers or safety enhancements; you become acutely aware that this circular justification by other-agents-predicting-your-actions is suddenly unavailable, and then when it's available again (five miles further on, you run across an old trail) the arrangement seems quite obvious.

As a final note, as in other games (like Prisoner's Dilemma) the payouts can be critically important to how we choose. As the problem is traditionally stated (always a thousand in box #1, either zero or a million in box #2), it actually makes the decision quite easy for us, even if we're worried about the fallibility of our brilliant alien benefactor (which again, if we are, then what's the point of this whole exercise!?!?). Making a decision that throws away a thousand for a crack at a million is not for most humans in Western democracies a bad deal. (If someone could show me a business plan that had a 50% chance of turning a thousand bucks into a million within the few minutes that the Newcomb problem could presumably take place in, I'd be stupid not to do it!) On the other hand if I lived in the developing world and made $50 a month and had six kids to feed, I might think harder about this. Similarly if it were five hundred thousand in Box #1 and a million in Box #2, things would be more interesting. Opening a box expecting a million and getting nothing doesn't hurt so much if you would have only got a thousand by playing it safe and opening both; it would be pretty bad if you'd expected a million and got nothing but could still have half a million if you'd played it safe.

Overall, the whole exercise of Newcomb's Box, as given, seems to me uninteresting and obvious. But enough smart people have gone on debating it for long enough that I must be some kind of philistine who's missing something about it. Nonetheless the arguments I've seen so far are not compelling; feel free to share more.

Public Health Ads Look Cooler in Basque

2010-08-08T02:39:00.000-07:00

Taken Donostia, Spain, June 2001.

Hints That You're Living in a Simulation; Plus, What Is a Simulation?

2010-08-04T01:29:00.000-07:00

See Bostrom's simulation argument for background. From a practical standpoint, you might be suspicious that you live in a simulation if you inhabit a world with the following characteristics:

Hint #1) Limited resolution. A simulation would be computation intensive. It would be useful to have tricks that increase the economy of operations, but in ways that do no compromise the consistency of the simulation to the players. One such trick would be to set an absolute upper limit to resolution (or a lower limit to the size of the elements that make up the "picture") that is below the sensory threshold of the players. These elements could variously be called pixels or quarks. Similarly, it would behoove the simulators to set a maximum time resolution, i.e. maximum frames-per-second, also called Planck times. Furthermore, the simulation's computing power is spared by a statistical method of calculating relationships between entities in the simulation (i.e quantum mechanics) even though it may look, at the scale of the game players or simulated entities, as if the universe maintained quantitative relationships in terms of integers calculated to arbitrary precision. (Related question: is it possible in principle given the physics of our universe for something the size of a bacterium or virus to "be conscious of" this gap in the behavior of the Newtonian and quantum realms, at a very basic sensory level? If not, isn't it interesting that our universe is such that there can be no consciousness operating on scales that would expose the twitching gears behind the scenes?)

Hint #2) There are limitations in what spaces within the game can be occupied by players or sims. In the old Atari 2600 Pole Position game, you couldn't just randomly go off driving off the track and through the crowd even if you didn't care about losing points; the game just wouldn't let you. Similarly, the total space in our apparent universe that we occupy, or directly interact with, or for that matter even get any significant amount of information from, is an infinitesimally small part of the whole. Unless you're in a submarine or in orbit, you don't go more than 200 meters below sea level or 13,000 m above it. (That's a volume of 2.1 x 10^18 m^3 that for all practical purposes the entirety of human history has occurred in; double that figure, and that's the volume that all of evolutionary history has occurred in.)

Hint #3) Beyond the "active game volume" as described above, dab a few pixels here and there in an otherwise almost entirely dark and empty volume. Make them so far away that sims can't possibly interact with them. Reveal additional detail as necessary whenever someone happens to look more closely at them. (And there's another trick: objects in this simulation are only loosely
defined until one of the players interacts with them, "collapsing the wave function". Yeah, that's what the programmers will call it, that's the ticket.)

Hint #4) Even in that limited location, make the active game volume wrap around. That way the simulators get rid of edge-distortion problems, as in Conway's Life. A sphere is the best way to do this. Therefore, work out the physics rules of the simulation to favor spheres.

Hint #5) Make each state of the simulation dependent on previous states of the simulation, but simplify by dramatically limiting the number of inputs with any causal weight. The simulators can limiting computations by having only mass, charge, space and their change over time determine subsequent frames.

Hint #6) If for some reason it is important for the entities in the simulation to remain ignorant to their existence as part of a simulation, the simulators could make sure the entities are accustomed to not only these kinds of stark informational discontinuities but to profound differences in the quality of awareness, both within themselves and each other. That is, the sims will accept not just that the vast majority of the universe (as seen in the sky at night) is interactively off-limits to them, but they'll also accept that their own awareness thereof and ability to connect the dots will dramatically vary over time. That way, if there is any need to interfere and make adjustments (to stop someone from figuring out the game) it won't strike the sims as strange. (Forgetfulness, deja vu, mental illness, drugs, varying intelligence or ability to concentrate on math, death of player-characters before they can learn too much?)

#6 does raise a very important question: why would the simulators give a damn if we knew we were in a simulation. So what? What would we do about it, sue them? If Pac-Man woke up and deduced that he were a video game character, if he still experienced suffering and mortality the same way, why would it matter? By this same view, there's an easy answer to whether we should behave differently if we're actually in a simulation: no. Whether our universe is in reality just World of Warcraft from the sixth dimension, if we simulated beings can suffer (and I know I can), then the moral rules are exactly the same as before.

It's also worth asking for some humility, and asking why we humans always assume that we would be the purpose of any such simulation. We could be merely incidental consciousnesses that are necessary for harboring the populations of simulated bacteria that the simulators are really studying. Or, the simulators could be cryonicists who preserve pets, and the most popular pets in their dimension look like what we call raccoons, and our universe is actually the raccoon heaven in which their beloved masked companions await a cure for the disease that forced the owners to put them on ice. In fact the raccoon-heaven simulation would contain a whole suite of ecosystem, all of them purely simulated (with the exception of raccoons) to keep up the appearance of a full biosphere. So the point of such a simulation would be to fool raccoons - or maybe even mice (again, why would they care about fooling everyone! If the simulators are reading this, just give me more juicy steaks and I won't make problems. It doesn't cost you anything!)

While the raccoon thought experiment is meant to be whimsical, a healthy respect for our own ignorance is always in order for these kinds of speculations. After all, assuming what we have guessed about the rest of (for the sake of argument simulated) universe is accurate, then there might be "aliens" (other non-human intelligences within the simulation) who may very well be much brighter than us. So even if the simulation is somehow arranged around the most intelligent entities within it (as we assume), those entities need not be human. Even if we're simulated, and we have a real brain and body in the "real" universe that's similar to our form in this one, this simulated universe might be designed for Martians (who are brighter than us) and be much less pleasant than our home dimension.

Finally, the very idea of a simulation is poorly defined. Mostly we think of something like almost completely controlled full-world simulation in the Matrix, but let's explore boundary cases. If I wear rose-colored glasses, is that a simulation (or a red world)? What about LSD that causes me to see unidentified animals scurrying past in my peripheral vision? What about DMT that causes a complete dissociation of external stimuli from subjective experience? What if I have some chip implanted that displays blueprints of machinery in my visual field a la the Terminator, is that a simulation? What about a chip that makes me see a tiger following me around that isn't there? (Hypothetical given current limitations.) What if I hear voices telling me to do things that are produced by tissue inside my own skull, by no conscious intent of anyone? (Not at all hypothetical.)

One of the interesting points in the popular movie Inception is the way that external stimuli appear in dreams. This gives us a hint as to what we mean by simulation, and why we care. Most of us have had experiences where the outside world "intruded" into a dream, with the stimulus obvious after we awoke. I once dreamed that a dimensional portal slid open in front of me with an ominous metallic resonance, and I stepped through it, suddenly speeding over the red, rocky surface of Mars. Then I realized it was my father opening his metal closet door in the next room, and I was looking into that room at the red-orange carpeting. Before I was fully awake I had received the sound stimulus but I had built a world out of it that most of us would not regard as real. (The experience of speeding over Mars was quite real, even if most humans would have a more accurate representation of that auditory stimulus.) So, a better way of saying "how do I know 'this' is reality, rather than another dream, or a simulation?" is to ask "how do I know I am perceiving "true" stimuli, without mapping them unnecessarily onto internal stimuli, giving me as accurate and un-contorted a view of the world as possible?"

And indeed in certain ways, we certainly are dreaming, in the sense of injecting internal stimuli and filtering external stimuli through them. (Notably, it is possible to view schizophrenics as people who experience dreams even while awake and filter their perceptions accordingly.) First and most obviously, because our sense organs are limited in what they can detect, we're obtaining only a slice of possible data. Second, the world we knit together is the result of binding of sensory attributes into object/events, as well as pattern recognition. The limitations of our nervous systems, and the associations we are able to make, profoundly influence the representation we build of the world we're perceiving.

Third, and most significantly, a large part of our experience is non-representational: emotions, pleasure and pain do not exist outside of nervous systems, or rather the events to which those experiences correspond are almost entirely contained within nervous systems. Yes, to be precise the experience of light does not exist until the triggering of a cascade of electrochemical events by radiation incident on pigments in retinal cells; but light, which is what is represented in our experience, exists traveling across the universe. Pain and happiness do not. These are internal stimuli that add a non-representational layer to reality, even more certainly than my dream of the Mars overflight.

A good working definition of a simulation as it is commonly understood is when the majority of one's external stimuli are supplied deliberately by another intelligence to produce experiences that do not correlate to physical reality external to the nervous system (or computational equivalent). This avoids taking a position on AI; the sims may or may not be entities separate from the computation. I.e., you might be in sensory deprivation tank like Neo, or you might be a computer program. The question of reality versus dreams or simulations is not one of discrete "levels" as we've come to think of it in popular culture. It is rather a question about how we know our experiences correspond in some consistent way with events separate from our nervous systems.

Looking for Neurological Differences Between Nouns and Verbs

2010-08-02T21:45:00.000-07:00

Just ran across this poster presented at the Organizing for Brain Mapping's Annual Meeting in 2004. Sahin, Halgren, Ubert, Dale, Schomer, Wu and Pinker looked at the fMRI and EEG changes associated with a number of language tasks, and one of the questions they asked was whether activation characteristics were different for nouns and verbs. This study did not find that they were.

In my sketch of a neurolinguistic theory, verbs are first order modifiers and are distinct from adjectives in that they mediate properties and relationships between nouns. (In this sense, intransitive verbs are more similar to adjectives than to transitive verbs.) I also postulate that nouns and first order modifiers should have identifiably different neural correlates. I have not yet completed a literature search (obviously, if I'm citing posters from 2004.) However, even if such different neural correlates obtain, then I think it the task design here was not necessarily adequate to capture such differences, because the participants were asked to morphologically modify the nouns and verbs in isolation, rather than in situ, in grammatical relation to each other.

Another interesting experiment would be to give the participants nonsense words and new affixing rules (i.e. not revealing the part of speech of the nonsense word, i.e. ("if the word has a t in it, add -pex to the end, otherwise, add -peg"), and look for any difference relative to neural correlates of morphological tasks done in real words.

Strong AI, Weak AI, and Talmudic AI

2010-08-02T20:49:00.000-07:00

Yale Computer scientist David Gelernter argues here that Judaic dialectic tradition will help us to reason our way through the moral morass of the first truly intelligent machine. I had first written this off as an article in the genre of "interesting collision of worldviews". But in the near future the cognitive science debates we're having today will seem luxuriously academic and unhurried, because for several reasons involving computing and neuroscience they will soon be more than intriguingly difficult questions. Even if we can all agree that suffering must be the basis of morality, we will need a way to know that, on that basis, it's not okay to disassemble someone in a coma, but it is okay to disassemble a machine that can argue for its own self-preservation.

John Searle Must Be Spamming Me

2010-08-01T04:39:00.001-07:00

Because with all the comment-spam, the waiting-to-be-moderated comments list looks like a Chinese chat-room. I have yet to see any Hindi. And anyway I'm sure the machine producing the spam doesn't understand the symbols.

Reflections on Wigner 1: Humility in Pattern Recognition - Mathematics as a Special Case

2010-07-28T12:21:00.000-07:00

It's often asked how natural selection could have produced something like the mathematical ability of modern humans. Why can an ape, designed to mate, fight, hunt and run on a savanna, and perceive things that occur on a time scale of seconds to minutes and a size scale of a centimeter to a few hundred meters, even partly understand quarks and galaxies? Implicit in this statement is an admiration for that ability, and the power of mathematics, as well as an assumption held by physicists that should not be surprising.

The physicists' assumption is that the whole of nature, or at least the important parts of it, can be described by mathematics. In "The Unreasonable Effectiveness of Mathematics in the Natural Sciences", Wigner observes "Galileo's restriction of his observations to relatively heavy bodies was the most important step in this regard. Again, it is true that if there were no phenomena which are independent of all but a manageably small set of conditions, physics would be impossible." Another way of saying this is that those regular relationships in nature most easily recognizable by our nervous systems are those parts of nature which we are most likely to notice first; seasonal agriculture preceded gravitation for this reason. But there is a circular, self-selection issue here about the interesting correspondence between the empirical behavior of nature and the mathematical relationships humans are capable of understanding, which is that:

a) humans can understand math.

b) What we have most clearly and exactly understood of nature so far (physics) employs math

c) Therefore, math uniquely and accurate describes nature.

Point b may be true only because our limited pattern recognition ability (even including infinitely recursive propositional thinking like math within that term) only allows us to recognize a certain limited group of relationships among all possible relationships in nature. In other words, of course we've discovered physics because those relationships are the ones we can most easily recognize! It's as if someone with a ruler goes around measuring things, and at the end of the day looks at the data she's collected and is amazed that it was exactly the kind of data you can collect with a ruler.

This discussion is far from an attack on usefulness of mathematics; if you have a model that worked in the past, bet on it working in the future, and the fact that not everything in the universe is yet shown to be predictable by mathematical relationships is certainly not cause to say "We've been at it in earnest for a few centuries and haven't shown how math predicts everything; time to quit." But it also certainly isn't time to say that math can show or has shown everything important, and the rest is necessarily detail. The whole endeavor of truth-seeking I think has at least something to do with decreasing suffering and increasing happiness, both very real parts of nature, and as yet there are very few mathematical relationships concerning them. I look forward to the day that such relationships are shown, but we cannot assume that they exist, or that if they don't, suffering is unimportant.

One problem is that if indeed there are relationships in nature un-graspable by human cognition or mathematics (and note that I've made no argument as to whether those two things are the same), how could we know? It would just look like noise, and we couldn't tell if a knowable relationship was there and had yet to be pulled out, or there was nothing to know (or knowable). We might at least know whether such unknowable information, or "detail", could exist, if we had some proof within our propositional system that there are statements which are true but cannot be deduced from the system. And we have just such a proof.

If we regard mathematics as a formalist does, that math is a trick of our neurology that corresponds usefully enough to nature, the question of why math is useful at all becomes even more important. But if we inject a little humility into our celebration of our own propositional cleverness, the matter seems less pressing.

We have no reason to believe that the total space of comprehensible relationships in nature is not far, far larger than what is encompassed by "mathematics", even in math's fullest extension. If this is the case, it is easier to see how our mathematical ability is a side effect of natural selection and the nervous system it created. By giving us a larger working memory than our fellow species along with some ability to assign symbols arbitrarily, that nervous system does allows us to use propositional thinking to see nature beyond the limitations of our senses - but just barely.

In this view, we can perceive just the barest "extra" layer of nature beyond what our immediate senses do, and mathematics seems far less surprising or miraculous. There is still reason enough to investigate math's unreasonable effectiveness but we shouldn't insist on being shocked that it could have been produced by the hit-and-miss kluges of evolution. But I've made another circular assumption here, which is:

a) evolution proceeds according to natural law

b) evolution will therefore favor replicators that have some appreciatiof some of those natural laws, and modify their behavior accordingly

c) therefore, our ability to perceive the laws that have impacted our own survival, and maybe a few extra ones of the same form, should be expected

There are two mysteries then: first, that any type of regular pattern exists in nature, and second, that we are able to apprehend these patterns, particularly through mathematics. The second mystery probably disappears, seeming special only because of the likely incompleteness of math as a tool to describe nature, math's special case as a method of perception stemming from our own neurology, and the circular basis of our wonder at this as-yet early phase in our use of it. But the first question, of how or why even partly regular relationships appear to exist at all in nature, regardless of how we perceive them, remains untouched by this essay.

In the Land of the Blind

2010-07-27T14:16:00.000-07:00

...the one-eyed man must remember the majority is always sane. The Country of the Blind by H.G. Wells explores how an entirely blind civilization might view the universe, and how sighted people might interact with them. The Churchlands' infra-people, while argumentative, seem quite diplomatic by comparison.

Redwoods Aren't That Ancient or Special

2010-07-25T12:58:00.000-07:00

Redwood Preserve in the Oakland Hills.

It's a common claim on informational signs in California parks that "redwoods were around at the time of the dinosaurs", or some such statement. While they're certainly amazing organisms, are these really tree-coelacanths?

Timetree consistently gives a divergence of trees in the order Cupressaceae (redwoods, junipers, various cypresses) at 80 MYA. We know from well-preserved fossilized trees that there were trees growing in the late Cretaceous that looked like modern redwoods, in the same place that modern redwoods grow. (This particular petrified forest near Napa, California is by far the most amazing petrified forest I've ever seen. I had to touch the trees to convince myself they're stone and not wood.)

Because fossilized "redwoods" date back to just after the putative divergence time, it's likely that modern redwoods are merely the more-ancestral-appearing descendants (relative to junipers and cypresses) of the these ancestral trees. Although the size and bark of the fossilized trees look similar to the redwoods today, that certainly doesn't tell the whole story about them, although barring miraculously preserved 65-million-year old Cretaceous tree DNA, that's about all we'll get. Consequently those old trees would more appropriately be called ancestral cypresses. Maybe the Ancient Giant Cypress?

Either way, redwoods are still pretty special, although not in the way that their chromosomes somehow resisted entropy for 65 million years.

Personal Genome Project Needs Volunteers

2010-07-05T00:27:00.000-07:00

Sign-up page is here.

Do Small Biotechs Really Produce More AND BETTER Drug Candidates?

2010-07-03T14:15:00.000-07:00

...and if so, why?

I occasionally post about biotechnology industry issues here insofar as they're relevant to the more central topics of this blog, and the productivity of the private sector biotech research enterprise directly bears on the tools we will have in the future to investigate cognition as well as to treat patients with cognitive and neurological disorders. If you're an academic scientist or philosopher and you find all this very dry, I would advise you to at least skim it so you can get an idea of what goes on in the evil world of industry. One thing I will say in defense of the private sector: workers are much, much better treated than they are in academia, not just in terms of money, but in working conditions and general treatment by superiors.

It's a cliche that Big Pharma can't find its own leads and has bought its pipeline from biotech for the past 10-15 years, which serves effectively as free-range R&D (until the round-up.) Having spent most of my time before medical school consulting at smaller biotech companies, and several times finding myself with free time because one of those companies was bought for its portfolio and closed, I've spent my fair share of time wondering about this question. However I actually can't recall seeing an analysis of biotech vs big pharma output, or in particular, of quality of candidates judging by ROI or absolute annual sales. But let's assume that the disparity is real. Big pharmas certainly do - they sometimes try to duplicate the perceived success of small biotechs by putting together small entrepreneur-like groups, like Glaxo. So what is it, exactly, that is more productive about small biotechs?

1) The most obvious: small biotechs have a much greater incentive to get their (usually lone) drugs into clinical trials - if they don't, they disappear. Big pharma management is not so incentivized, and timelines of individual drugs are sometimes adjusted to fit the portfolio. What's being maximized is completely different for a start-up biotech and a multi-drug big pharma. Overall sales is what's being maximized in big pharma, while speed to first-in-human and to market is being maximized in biotech (it equates to survival and therefore financial incentive.)

2) Small biotechs may produce more candidates, but on average lower quality candidates. Because of money and therefore time limitations, they're willing to push through the first lead where the Glaxos of the world have the cash to keep tweaking the structure. You would think this would necessarily mean that the big pharmas then wouldn't be interested in these low-quality candidates, but a) not all decisions are rational, and hype and groupthink have effects in the real world ("We have to buy them to get the first XYZ inhibitor!") and b) the first-in-humans candidate of a given class is often "lower quality" than what might have been the second-in-humans, which as mentioned the biotech won't wait around to discover; the perception and impact of the quality difference is highly context-dependent.

3) At biotech start-ups, scientists have the greatest influence on senior management or are senior management. Typically the management of the group closest to revenue generation is the one that has the most influence over the CEO. In big pharmas, this means sales. In a company that doesn't yet have any sales, this means clinical, or (if even earlier in the cycle) chemists and biologists. Once sales obtains this position, the amount of time the CEO spends thinking about sales increases and development plans tend to be de-emphasized (until everyone panics and it's too late.) I had long suspected that Genentech's success owed to its keeping scientists in key decision-making positions and after having consulted there I'm convinced that this is the case.

4) There are scale-dependent effects that would be present in any organization but are exacerbated by the uniquely long product development cycle in pharmaceuticals. Another exacerbation is the level of government oversight in the industry and the consequences of regulatory transgressions, leading to what are referred to in politics as Olsonian veto blocs, large groups of people who have a say in the process and have nothing to lose by saying "no" but everything to lose by saying "yes" at an inappropriate time. In the pharmaceutical world this is legal, regulatory, and QC - absolutely necessary to the industry, but their influence on timelines seems to be strongly scale dependent. In my own experience in the industry, some of the most focused "how do we get this done" people I've worked with were in QC at the biotech level. Some of the most obstructionist were in QC at the big pharma level. In general a company with a large revenue stream should be expected to be much more risk averse than a company with no profits. In the same vein, once a drug is approved, any new investigations could potentially yield a new indication that would provide some new revenues, or new safety findings that would diminish revenues across the board for the whole molecule, so post-marketing investigations are usually done with kid gloves.

5) Again scale-dependent are free-riders. At a smaller company, free-riding is obvious to all, more immediately detrimental to the future of the entire company, and more quickly punished. This is not the case at large companies with deeper pockets, many of the employees of which seem to be benefiting from a kind of corporate welfare state. This situation often arises at low surface-area-to-volume companies, where most employees interact only with other employees rather than with customers, vendors, or industry contacts outside the company. It would be worth seeing whether there's a sweet spot for company size in terms of a relationship between number of personnel vs. first-in-human clinical trials per person*year, including outlicensed compounds. Anecdotally, I have also noticed an odd scale-dependent increase in the proportion of people who have ever worked in government - not from related agencies like FDA, but from local governments or other areas.

[Story time - and if you know me personally, you know which company I'm talking about. I couldn't help but reflect that the strategy of employees of one big pharma subsidiary company where I worked was exactly that of a parasite in the gut of a large, warm mammal that can afford to miss a few calories here and there. They downside to the strategy is that they're super-specialized to thrive only in that environment; that is, their skillset degenerates into "how to stay employed at ABC Big Pharma". Consequently sometimes they have to transfer between mammals of the same species (i.e. subsidiaries) to survive. They day it was announced this particular subsidiary was being shut down by the parent, I saw groups of people openly weeping as if Princess Diana had died all over again.]

CONCLUSION

If you didn't get enough speculation already, read on. Plus this part also has colorful analogies that I think are nonetheless still useful.

- Dunbar's number applies to organized humans in all activities. There has been work done on Amazonian hunter-gatherers showing that there are village sizes beyond which there tend to be fission events. It's not that the village hits 150 and everyone draws straws to determine who moves, but there are dynamics that invariably take advantage of a trigger event to cause the split (the chief and his brother have a fight, there's a food shortage and some families move to find better hunting areas, etc.) This suggests that there are in general optimum sizes for human social organizations. This research may have a direct bearing on the productivity of small vs. large companies.

- The biotech industry in each part of the country where there is an active scene (the Bay Area, Seattle, San Diego, and Boston) is a notoriously small world. People often end up working together in different combinations at different companies, merely being re-sorted based on skillsets. In Edward Bellamy's 1888 utopian novel Looking Backward, he describes a system where workers have general industrial skills and are (centrally) resourced to new factories based on need. Of course Bellamy was arguing from a socialist standpoint but in biotech it seems that the free market has already generated exactly this arrangement.

- The pharmaceutical industry is not the only one that is dominated by deep-pocketed century-old behemoths that present barriers to entry and snap up competition as it first evolves from the primordial slime and takes its first stumbling steps in an established jungle. If biotechs are as everyone expects more productive than big pharma, this is bad for patients and bad for the economy, and yet there is no check on the growth of the largest companies. It's as if we're at the end of the Cretaceous (with animals so large they need second brains to coordinate their movements) or in the middle of the Second World War (where the incentive to build ever-bigger battleships yielded the monster Yamato.) In both cases, conditions changed (climate and aircraft, respectively), and selection no longer favored the most massive, but it's hard to see how this trend will ever reverse itself, since it's hard to see how capital accumulation can ever be economically selected against. That is, I don't know what would be capitalism's equivalent of Chicxulub or P-51 Mustangs that would obviate the uneven accumulations of capital, so for now we're stuck with biotech serving as free-range R&D for big pharma.

This is cross-posted with a different introductionj at my economics and social science blog, The Late Enlightenment.

Failed Alzheimers Trial Data Pooled and Made Available

2010-07-03T12:40:00.000-07:00

Biopharmas that have had failed Alzheimers drugs are pooling their data in an archive. This is excellent news for several reasons. First is that sharing data means a better chance at success in the future in this very therapeutically tricky disease that has sent more than its share of clinical programs to their graves.

This is a solution I hope we see employed outside this one disease. Several times I've been working on molecules that were killed either because there was a business case (didn't fit in the portfolio; acquisition occurred and acquirer only wanted other drugs from our pipeline, market changed during development, etc.) or scientific reasons - there were toxicities, or we found another molecule that was better. But it was always frustrating to think, particularly in the case of acquisitions, that the data was locked away on a server somewhere never to be seen again, and potentially of scientific use to future research programs. For Alzheimers at least this is no longer the case.

A secondary benefit is that the debate of pharmas "hiding" negative trial data will be quelled, again at least for Alzheimers. The failures will all out there for everyone to learn from.

Why Modern Music Is Too Hard, But Visual Art Isn't

2010-07-02T23:25:00.000-07:00

An interesting piece in the New York Times discusses why much of the last century's classical composition and dense prose may never find an audience, but at the same time visual modern art presents a more effortlessly coherent experience. The definition for complexity in music is given as non-redundant events per unit-time, but I'm not sure how they're measuring pattern recognition challenge in visual art and prose. The money quote in the article has to do with why it's much easier for the un-initiated to enjoy a Pollock piece:

The word "time" is central to [critic ]Mr. Lerdahl's argument, for it explains why an equally complicated painting like Pollock's "Autumn Rhythm" appeals to viewers who find the music of Mr. Boulez or the prose of Joyce hopelessly offputting. Unlike "Finnegans Wake," which consists of 628 closely packed pages that take weeks to read, the splattery tangles and swirls of "Autumn Rhythm" (which hangs in New York's Metropolitan Museum of Art) can be experienced in a single glance. Is that enough time to see everything Pollock put into "Autumn Rhythm"? No, but it's long enough for the painting to make a strong and meaningful impression on the viewer.

In a word, the constraints of sensory memory, determined by the sensory modality which is being used (hearing, vision, language, etc.)

Rapid Evolution in Tibetans - and Who Else?

2010-07-02T10:50:00.000-07:00

Science paper isn't up yet but probably will be by the time you read it. Tibetans only split from Han less than 3,000 years ago and already they've built up a whole repertoire of genetic low-oxygen adaptations.

While that may not be a surprise, the speed with which it occurred probably is. More and more, it's becoming clear that cultural choices we make (what we eat, where we live) over time affect our genes. So this leads us back to the elephant in the room of human evolution studies. There are genes which affect cognition. Why do we think these haven't been selected differentially as well?

Pattern Recognition in Numbers and Tiles

2010-07-02T01:21:00.000-07:00

All numbers can be represented accurately with an infinite string of digits, whether they are rational or irrational. This seems trivial for rational numbers and especially for "round" numbers, but it's easy to be confused by writing conventions and the coincidence of numeric base that we use. In base-10, we omit zeroes, so that 1.5 is really 1.50 with repeating zeroes to infinity. There's no information in the infinite string of 0's so we can omit them and still accurately represent the number (we compress it by writing the repeating parts in shorthand.) As for "not round" rational numbers, the vast majority of their patterns will not be immediately obvious to humans, given our limited pattern recognition limitations and the numeric base that we use. In base-10, the ratio that produces 0.142857-repeating is not obviously 1/7, but in base-7 it is - because in base-7, it's 0.1.

Some numbers have been proven to be irrational. The earliest of these for which we still have a record was Euclid's reductio ad absurdum for the square root of 2. The same has been done for pi and e, among other constants; but as yet, there is no generalized method for proving a number's irrationality.

A proof that there can be no general method for proving a number's irrationality, or at least whether the irrationality of some numbers may never be proven, would be worth having. Using a very unorthodox practical proof: there are finite particles in the universe with which to compute these numbers, and they will exist for a finite time; not nearly long enough to run through all the operations to produce ratios even for all the (infinite) irrational numbers between 0 and 1, regardless what those operations are.

What is interesting about this problem is that ultimately, proving rationality means recognizing some periodicity (or for irrationality its absence) and therefore that more generally proving ir/rationality is a pattern recognition problem. Other problems which are essentially pattern recognition problems are Kolmogorov complexity, i.e. compressibility, which although archiving applications do it all the time is in an absolute sense non-computable; and tiling problems, infinite (plane-covering) solutions of which are famously shown to be undecidable in principle by any algorithms. Are there other properties that these non-computable pattern-recognition problems have in common?

Could the Flynn Effect Be the Result of Decresed Parasite Loads During Pregnancy?

2010-07-01T09:16:00.000-07:00

Paper here. The paper is looking at differences between IQs based on current epidemiological stats, but it seems the next step would be to look at differences in the same population over time. The policy implications need not be stated. Via Dienekes.

Dreaming About Former Stress Experiences

2010-06-30T00:50:00.000-07:00

It's a cliche that in the industrialized world, adults tend to dream about missing exams in high school or college. You know the ones - you have a test or a class you have to be in but you don't know where it is, the hallways don't make sense, your school or the buildings aren't the way you remember them, and it's a disaster. You wake up and you're maybe even mildly amused; thank goodness you'll never have to deal with that again. Why do we seem only to have these dreams when we're no longer in that situation?

After a 13-year hiatus from education I began medical school at age 35, leaving a career in biomedical research consulting. At one point prior to starting med school I joked to a colleague that I could no longer laugh off those missed-exam dreams because there are many, many more quite real exams in my future. But what I am amused by is that now, I no longer have missed-exam dreams, and instead I've started having anxiety dreams about situations associated with my pre-medical school career. Usually, in these new dreams, I'm arriving late at an airport only to find out that my flight has just left. That this change occurred less than a year after I left that career certainly suggests that there's some mechanism which pegs anxiety to stress experiences that we no longer have, or that are associated with some earlier phase of our identities.

What could be going on here? There are lots of people that change careers and/or go back to school, so has anyone else had this experience?

Hupa is Not Unique Among Languages in its Use of Verbs

2010-06-25T14:58:00.000-07:00

In a sketch of a neurolinguistic theory I posted previously, I mentioned a possible empirical problem with the theory. Specifically, I posit that the basic neurological unit of language is the noun. If this were the necessary structure of language based on human anatomy, a non-noun-based language would falsify the theory. The Wikipedia article on Hupa previously stated:

Morphologically, it is remarkable for having an extremely small number— perhaps less than one hundred— of basic (monomorphemic) nouns, as nearly all nouns in the language are derived from verbs.

I have long been interested in Hupa as a result of this statement. The first question we might ask is whether such a dramatic innovation is restricted to Hupa or in fact appears in some form in other lower or Pacific Athabaskan languages. There is no report of such structures in Upper Umpqua or the Rogue River languages.

Once you read the grammar and vocabulary of Hupa published by P.E. Goddard, 1905, barely half a century after their first contact with Europeans, the answer was clear. The claim about Hupa's use of verbs and paucity of nouns, which is not referenced, is totally inconsistent with Goddard's work. Goddard lists 130 nouns straight away in the first 20 pages. Not all are morphophonemic, but the non-compound morphemes for the obligately affixed nouns seem to all be unique. Furthermore there is discussion of verb nominalization on page 21-23, and while the morphology seems to be more elaborated than in Western Indo-European languages, it's nothing as dramatically novel as this statement, certainly not showing that "nearly all nouns in the language are derived from verbs." In fact Athabaskan languages in general have elaborate verb morphology, though again, they don't replace nouns.

For a time I had thought that Hupa was a real-life example of the fanciful verb-based language of Tlön fantasized by Borges in Tlön, Uqbar, Orbis Tertius. But it's not. It's worth pointing out that there does seem that there are some innovations of Hupa, relative to other Athabaskan languages, but this is to be expected from a language isolated for centuries with close trading relationships with an Algonquian language (Yurok) and a probable isolate (Karuk). Certainly the differences are not so profound.

I subsequently revised the Wikipedia article. In the meantime continue to look for languages that falsify the neurolinguistic sketch. One interesting possibility is that we might find dramatic differences in language based on geography with phylogenetic patterning. That is, is there something different about Andamanese + New Guinean + Australian languages (earliest out of Africa) vs. sub-Saharan African languages vs all other languages? I'm not asking whether there could be differences based on language-descent, which there necessarily will be; I'm asking the far more controversial question of whether they may be genetic innovations that result in different wiring and therefore differences in language structure. So far we have not found differences so profound as to warrant speculating about population-wide differences in the underlying hardware. If we ever do find differences in a language or group of languages as dramatic as the one that had been suggested here, or that Daniel Everett suggested with Piraha (which also appears to collapse under scrutiny), I submit that it might be profitable to look for anatomic and genetic differences. Such diversity of language and neurology would absolutely be a windfall to understanding the physical basis of language and cognition.

As an aside, I have been to the Hoopa Nation in Northern California several times. It's absolutely beautiful country and I highly recommend a visit. Unfortunately the Hupa language is not a living language, although it is being preserved by the efforts of Danny Ammon and others who make their resources available for the rest of us.

Trinity River south of Hoopa, California, by Trinityalpsphoto

Cranial Blood Flow Differences Between Populations?

2010-06-25T12:16:00.000-07:00

A provisionally published paper in BMC Research Notes by Farhoudi et al uses transcranial Doppler to investigate flow rates in major cerebral arteries. They found that the averages for their sample from northwest Iran were higher than previously described norms.

The numbers are presented as-is with no p-value, so caution is in order in thinking these are necessarily real (though Farhoudi et al don't make any claims beyond presenting the numbers.) What is immediately interesting is whether there are real population differences and what that means for investigative methods like fMRI studies. There's also the question of whether there are clinical correlations (different stroke rates and outcomes in some populations?) or even behavioral/cognitive connections - though for that last question I'll hope that Razib Khan picks up the story.

A Competition Mechanism for Attention

2010-06-25T10:48:00.001-07:00

A nucleus in the midbrain of owls is found by Asadollahi et al to encode salience (i.e., relative strength) of visual and auditory stimuli. This is strong support for the existence of the previously theorized salience map and is a big step in the study of attention. Nature paper here.

Future questions: how is remote sense data (visual-auditory) integrated with contact data (touch, pain and taste)? How are attention conflicts resolved; that is, when an agent voluntarily wants to focus on a stimulus that is weaker and no more irregular than those around it? In the case of humans trying to focus on one visual stimulus known to be important despite sensory distraction, might we predict inhibitory projections from the temporal cortex to this nucleus or to its projections?

DNA Testing and Inconsistent Laws

2010-06-13T09:07:00.000-07:00

The following seems a little bass-ackwards: FDA doesn't regulate companies that sell bullsh*t medicine - that is, "herbal supplements" which these highly profitable companies strongly imply can treat disease (and are sometimes unsafe, just like real pharmaceuticals.) But this same agency is now warning DNA testing companies that they're out of compliance, even for products that aren't intended to diagnose disease. I have two 23andMe kits sitting in my office right now that I haven't sent in yet, and I'm going to be pretty annoyed if FDA's ruling affects them. I suspect I'm not the only one. Following FDA submission rules is enormously expensive and time-consuming, and most of these companies don't have the resources to do it. Unless we think of a sensible solution, good-bye DNA testing industry.

This personal genomics/personalized medicine revolution everyone is talking about won't get her if it's made illegal. The problem is not that there should be no regulation, it's that there should be consistent, non-stupid regulation, and the U.S. is going to damage a domestic industry that will be very important in the near future early in its development.

[Added later: Alex Tabarrok at Marginal Revolution says it much more elegantly and directly: "The idea that the FDA can regulate and control what individuals may learn about their own bodies is deeply offensive and, in my view, plainly unconstitutional."]

The Loneliness of the Seminal Computer Scientist

2010-05-31T20:49:00.001-07:00

(Granted, Sillitoe's story has a better ring to it than the title of this post.) Probably already well-known among modern mathematicians and computer scientists, Alan Turing was quite an accomplished distance runner. When I first saw his 1947 Lecestershire marathon time of 2:46, I thought there might be some confusion; Europeans use the term "marathon" much more loosely than North Americans. On this side of the Atlantic, a marathon is 26.2 miles, period. So I looked it up and there's even a newspaper clipping image which specifies that yes, this is a real marathon time. 2:46 would be a damn good time in 2010, let alone in 1947 with bad running gear and probably bad nutrition and training. My own PR is 3:13 and I will likely never approach Turing's time regardless how much EPO and 'roids I consume.

Hemineglect and Delusions

2010-05-23T00:43:00.000-07:00

Hemineglect is among the more bizarre neurological conditions (which is also to say, devastating to the patient). In brief, the patient ignores one or the other half of space, right or left, up to and including his or her own body. They won't register stimuli on the neglected side and will even ignore their own bodies on that side, sometimes claiming that their limbs aren't their own: if you hold their arm up in front of them and ask them whose arm it is, they'll often insist it's a family member who's hiding nearby. (Yes, really.) A neurologist related to me that these patients will even sometimes request to be moved to a new bed in the hospital because there's someone else laying in bed with them (as in, the neglected half of their own body. Yes, really.) To these patients, a circle has only 180 degrees. The neglected half of space might as well be the fourth dimension.

Needless to say, natural experiments like these cases are a rich substrate for neurophilosophy. One aspect of neglect syndromes that I find interesting is that some of this behavior apparently amounts to a delusion, in the strict sense of a steadfast false belief. Neglect patients will sometimes complain that the hospital isn't feeding them enough, and of course when the nurse or physician comes into the room, they see a plate of food that's exactly half-eaten. So they turn the plate 180 degrees - and the patient grumbles "Good," and continues eating. See the disconnect here? If I were at dinner and said "Wow that green curry was good but I wish there were more," and my dining companion was able to magically produce more curry out of the fourth dimension before my eyes like some kind of a 3D chef visiting Flatland, of course I would be utterly amazed - but I haven't heard of such a reaction in the anecdotal reports I've heard from neurologists so far (I have not yet interacted with a neglect patient).

I'll do my best to put myself in the neglect patient's place again. Most of us believe that we have exactly 2 arms and 2 legs, and would react incredulously if a researcher told us that no, in fact we had four arms and four legs, but we were only using two of each. The researcher says to me "Fine, I can prove it." In an empty room with just her and me, she holds up an arm in front of me that looks just like me other two arms - skin color, size, etc. - and says it's my arm. I can't feel it or move it, and somehow I'm unable to see what it connects to, and it seemed to appear out of thin air (just like the green curry). But having four arms is ridiculous! Yet I trust this researcher; she seems incredibly earnest, she can reproduce this trick any time I ask with no preparation, and as I soon discover, so can anyone else I ask, including people with no possible connection to the researcher. All of them can hold up in front of me one or two arms that look like my own arms.

In such a position, I would be forced to conclude, as bizarre as it seems, that the evidence points to some kind of a perceptual defect on my part. As strange as it is, and as much as I absolutely cannot understand where this arm is coming from or how it connects to me, I eventually have to accept the incredible truth (after many, many trials) that I and everybody else has four arms, and that there's something strange about my perception that keeps me from seeing them. And even if I remain incredulous, certainly I would at least want to know how they were doing this amazing trick. But severe neglect patients not only avoid curiosity about things that could disturb their limited perception of space, they make up impossible stories about where their limb is coming from if it's presented to them. Clearly the deficit that produces their inability to fully represent space is neurological, rather than psychogenic. But isn't this part of the behavior arguably delusional?

Ultrasound, Neuronal Excitability, and Hallucinations

2010-05-15T01:12:00.000-07:00

A few years ago it was announced that a U.S. patent had been filed by Thomas Dawson on behalf of Sony for direct neural input of sensory information. There are a few: the most recent related patent by the same inventor here, but the one that I believe attracted media attention is here).

The patents describe a method of stimulating multi-modality sensory experience through the use of sound energy. The basic idea is that neuronal excitability can be increased with ultrasound (review here) although to date it seems that all the work has been either with CNS neurons in culture, or PNS neurons, rather than CNS neurons inside a spine or skull. Obviously if these patents represent functioning technology the implications are profound. For that reason I scrutinized 6,536,440 for evidence that the concept had in fact been reduced to practice, which (naively I'm told) I had thought was still a requirement for the issue of a patent. There's precious little in the document to suggest anyone is ready to build a transducer capable of producing any sensory experience in subjects, let alone a coherent one.

Of course ultrasound is already used in medical imaging all the time, in a similar range to that reported in the review (optimal transcranial transmission of ultrasound at 7 x 10^5 Hz, but in vitro studies showed neuronal excitability changes at higher frequencies around 2-7 x 10^6 Hz. Medical imaging ultrasounds use frequencies up to 10^7 Hz, but the intensity range is 1-10 W/cm^2, and the imaging device is rarely applied to the skull (useless for imaging, because bone blocks commercial ultrasound). That said, I'm unaware of anecdotal reports of patients hallucinating by any modality during ultrasound imaging, a very common outpatient procedure, and quick search of Pubmed reveals no such cases among the first 30 articles.

A Possible Mechanistic Answer to Penrose et al

2010-05-09T21:07:00.000-07:00

Paper here, "Informal Concepts in Machines", Kurt Ammon. Argues that algorithms exist which can perform computations beyond the limits of Turing machines. This is one answer to the problem of how, if humans are machines, we can definitively decide non-computability (one of Penrose's challenges).

Junk DNA and Cancer

2010-05-02T21:24:00.001-07:00

In Nature Lamprecht et al provide evidence that the presence of long terminal repeats (LTRs, a form of junk DNA) increases the risk of humans' developing certain cancers, especially lymphomas. [Added later: in 2007 the ENCODE study was supposed to show evidence that intragenic regions are pervasively transcribed but there's a large segment that believes this to be an artifact.]

Initially the discovery that our genomes were to a first approximation entirely composed of non-coding garbage characters was a surprise. But on further evolutionary reflection, it made sense: DNA is about copying itself, and it sometimes codes for proteins in networks with other pieces of DNA as a replication strategy. Consequently we should expect that most DNA is passively or selfishly just along for the ride, except in highly fecundity-dependent species where the extra time and energy make a fitness difference (like bacteria). Before you make the effort to back-of-the-envelope calculate the daily cost of replicating the 97% extra noncoding portion of our genome, realize that I have doubtless expended more calories typing this blog post than I will expend from all the DNA replication and proofreading I do during the entire day.

But even if the energy expended is not a problem, this paper revives the debate, because it shows that there still is a fitness cost for junk DNA in multicellular organisms - but it's paid in terms of cancer risk rather than energy cost. It's a little harder to write this off as fitness noise. We're back to the old question of what the advantage is for multicellular organisms to carry so much junk DNA.

Predictable But Still Interesting Resolution to Bilingual Coma Case

2010-04-30T11:43:00.000-07:00

I had previously written here about the case of the Croatian girl who supposedly woke from a coma miraculously speaking German. Of course, it turns out she already spoke German before. It's still neurologically interesting that ability in one language would be preserved than the other; Steven Novella covers.

Medication Resources, Psychiatric and Otherwise

2010-04-29T19:21:00.000-07:00

I promise a return to a less med-school-centric blog tomorrow. For now, in keeping with the theme, here are some interesting resources for medications and patients:

Psycho-Babble - a discussion forum about psychiatric medications. While it seems on its face like it could be a bad idea, strong moderation keeps it valuable and on-track.

Patients Like Me - a forum where patients can share their experiences with medications. Probably not a place to get real data, but nonetheless it might be worthwhile for marketing and healthcare workers to check out occasionally to see what the dominant threads are. General, not just for psychiatric meds.

For Second Year Med Students

2010-04-29T17:34:00.000-07:00

The boards are coming up (as if you need someone else to remind you of that) and if your pathology isn't quite up to snuff, here's a Magic: The Gathering-style fantasy role-playing card game to help you memorize all the nasty unicellular beasties. Here, of course, is B. fragilis:

I think these guys were just huge nerds who wanted to make money by creating their own card-based RPG while seeming all responsible and mediciney. And good on em! (Hat tip Boing-Boing).

Top Psychiatric Prescriptions for 2009

2010-04-29T12:31:00.000-07:00

Can be found here. While not of philosophical or scientific interest, it's certainly of professional interest to nervous system health professionals to ask to what degree the revenue growth is due to off-label use (at a guess, much more than half. Also note the comparison to simultaneous population growth).

Before starting med school I did clinical research for pharmaceutical companies for 12 years. In no polity that I know of can a drug be marketed "in general", that is, beyond some narrowly defined indication. Consequently the pattern of use of psychiatric drugs is very different than for other therapeutic areas. But they can certainly be used by practitioners this way. Is this inherent to the nature of psychiatric illnesses, or is it just an artifact of our regulatory enterprise? What risks are there to patients as a result of this pattern of use, and have we already seen an impact?

Croatian Girl Wakes Up from Coma Speaking German

2010-04-25T18:34:00.000-07:00

This is more dramatic than "foreign accent syndrome", although the story is short, the source suspect, and even without those two de-weighting considerations I would highly doubt it's real. I would put money down that we're going to find one of the following:

1) It's exaggerated, and at most she has some form of foreign accent syndrome.

2) The girl spoke German before she was in a coma.

Free Will and Materialism or Epiphenomenalism are Not Mutually Exclusive

2010-04-24T23:05:00.000-07:00

Some materialists are a little too eager to claim that free will is necessarily exploded if our consciousness is based in the material world and follows lawful processes. Of course this has implications for morality. However such an eager deconstruction is simplistic, and furthermore cannot be specifically pinned on
epiphenomenalism.

Regarding the possibility of free will, we recognize the following categories of relationships between any discrete entities in the universe, which must include conscious entities like humans:

1) Lawful relationships: if operation X happens to entity A, then B always results. It is not trivial to note that knowledge of lawful relationships must result from repeated pattern recognition. It is frequently pointed out that after building his system of mechanics, Newton loudly proclaimed what he saw as a pre-determined clockwork universe; despite this he somehow avoided moral nihilism.

2) No relationship (noise): a failure of pattern recognition. Perhaps there is no pattern, or perhaps there is but we're too stupid to see it. Whether there is a generalized way to tell the difference between these two possibilities without knowing the pattern if one is determined exists is another question. Note that nuclear decay is lawful only en masse but at the level of individual nuclei is random; quantum mechanics famously emphasizes the non-predictable (non-lawful) behavior of individual particles. Matiyasevich showed more generally than Goedel that all systems must contain detail, that is, true statements that cannot be deduced by the axioms always exist ("details"). But this still doesn't get us out of the woods because intentionality is not random.

3) Free Intentionality: Goal-seeking behavior that is not random but not forced by physical law to make the specific choices it does. This is most consistent with the folk model of behavior. Many materialists would claim this is a myth forced on us by our own neurology, and that there is no space for any options besides 1 or 2.

There are several answers to the problem of free intentionality that do not involve an appeal to faith ("i.e. It seems true so it must be"): yes, it does seem true, and while the preceding statement isn't the end of the argument, certainly it's premature to assume that free intentionality must be an illusion because our understanding in 2010 of the way the world works doesn't allow for that class of actions. (Note Newton's smugness.) We have nothing close to a complete understanding of the nervous system, so it's a little soon to be discarding introspection.

Grant for the moment that such a thing as free intentional behavior exists. I would argue (separately) that the property of free intentional behavior exists more in some entities than others, and that this property is lawfully determined. It is less clear exactly what those properties must share in order to exhibit free intentionality. Importantly, must free-intentional entities have experience; that is, can "dead" systems or much less advanced systems like cnidarians have free intentionality but not be subjectively aware? Because we're talking about humans in these discussions the assumption is that we would have both free intentionality and experience, but if an argument has been made that they must co-occur, I haven't yet seen it.

Epiphenomenalism

The bogeyman of free will is whether consciousness is an epiphenomenon of the real process of cognition, like a shadow or aftereffect. In some cases it certainly is: EEG studies have shown that people often decide to make a movement up to 300 milliseconds before they do, and the experimenter watching the trace literally knows before they do that they're about to move. First, because this is sometimes the case does not mean it is always the case.

Second, and more critically, why is it so troubling if our consciousness is on a tape delay? Assuming free intentionality applies to your nervous system, but not to your conscious awareness (if it's epiphenomenal) then you subconsciously have free will and become of a free intentional decision after it was made. In one sense "you" are just along for the ride, but it's a ride on a computer with free will that has been telling "you" what to do in a deceptive way since the day you were born and which cannot be separated from "you" without the end of your experience (because that means cutting your brain out). As long as the inseparable computer that's giving the orders has free intentionality, we have no right to be upset by the arrangement. The key to whether we can make free intentional acts is therefore not in the length of the tape delay, but in the behavior of the computer that's making decisions for "you". Our understanding of the nervous system does not yet allow us to rule out category #3 above, especially in light of strong introspective
evidence.

IF FREE INTENTIONALITY DOES NOT EXIST, WHY DOES IT SEEM LIKE IT DOES?

1) If free intentionality is in fact an illusion - why? Why would it be useful for organisms to deceive themselves into thinking that they have free will? The same question can be asked of conscious experience itself. How could such a thing be evolutionarily selected for, since it seems to have no outward manifestation?

2) For those who believe in a pre-determined universe, this means we're living in a static four-dimensional block of space-time. Why does "now" seem to be a special point in time? By this view, "now" is an illusion. How could organisms have developed that do not sense the full sweep of their existence? Why would this narrow focus on a gradually-shifting, illusorily-special space?

3) Free intentionality seems to manifest more at greater time scales. It is clear that there are behaviors resulting from Category 1 lawful relationships in every organism, including ourselves. If there is free intentionality, it a) probably occurs at least in the executive decision center and b) manifests over longer periods of time. Case in point, tell a person they have no free will and a common response is to hop on one foot or do something else socially unexpected. Find that person in exactly one month's time, and try to measure how different their life is because they hopped on one foot for five seconds; not very much I'll wager. It's the person who is making considered decisions based on semantic reasoning whose life can change over time. If free intentionality exists anywhere, it is in this kind of cognition.

ADHD, Dopamine, and Nomadism

2010-04-21T10:27:00.000-07:00

My uncle Bill was one of those guys with "too much energy". Among other things, starting at age 10 he would climb out his bedroom window at 1 in the morning, walk on the train tricks to the city ten miles away, and be back in bed before dawn. My grandparents only found out about his nightly forays when the police found him outside at 3 a.m. What's odd is that I've heard of several others engaging in this exact same behavior - sneaking out at night to follow train tracks or paths.

This level of restlessness doesn't necessarily require a diagnosis but the repeated pattern is still striking. You can't help but wonder what gives some people this kind of energy and why it expresses itself in terms of "exploratory" behavior. One possibility is that these individuals are acting out behaviors which were adaptive at one time, and that in fact these are goal-less random walks of the sort that predators engage in to find new hunting territory. That I know of, none of these individuals were diagnosed ADHD, but it certainly brings to mind the hunter-farmer theory. It would be very interesting to genotype these individuals for DRD4 polymorphisms, since a) there are DRD4 alleles associated with ADHD (7R) and b) in one African population split between farmers and nomads, the 7R allele was associated with greater stature and weight in nomads, but not in sedentary farmers.

The next step is to look at behavioral correlates of the DRD4 allele. In particular:

1) Ability to tolerate pain or negative stimuli while pursuing a goal, DRD47R vs non-7R. This may be a way to measure the lay term "hyperfocus", to see if it's real and if so, how and to what extent it manifests in 7Rs.

2) Comparative activity of reward circuity in DRD47Rs to non-7Rs, perhaps by fMRI. An fMRI study has already been done correlating 7R, reward circuity activation from food, and weight gain.

Of interest to readers mostly for humor: I already know from an ethnic genotyping study that I have a DRD1 mutation, and although it was novel at the time to the big databases, it was in the middle of an intron so it probably has no effect. But I haven't yet been sequenced at my other receptors and plan two within the next two years. I would put good money on having at least one 7R. Given the greater food rewards, this only supports my argument that people with good manners just don't like food.

NYT Article on Psilocybin Research

2010-04-17T12:36:00.000-07:00

Read it here. It's good to see that laws which are meant to protect people's health are finally allowing important research to go forward instead of obstructing inquiry for no good reason.

Neuroanatomy: There's An App For That

2010-04-16T22:40:00.001-07:00

Cerebrii is a 3D neuroanatomy application for iPhone. Read and download here.

The Universality of Word Boundaries in Human Cognition

2010-04-15T17:37:00.001-07:00

"...Twice I have taught intelligent young Indians to write their own languages according to the phonetic system which I employ. They were taught merely how to render accurately the sounds as such. Both had some difficulty in learning to break up a word into its constituent sounds, but none whatever in determining the words. This they both did with spontaneous and complete accuracy. In the hundreds of pages of manuscript Nootka text that I have obtained from one of these young Indians the words, whether abstract relational entities like English that and but or complex sentence-words...are, practically without exception, isolated precisely as I or any other student would have isolated them. Such experiences with naive speakers and recorders do more to convince one of the definitely plastic unity of the word than any amount of purely theoretical argument."

- From Language: An Introduction to the Study of Speech. Edward Sapir, 1921.

What Does the Autonomic Nervous System Lack? What Do Birds Have?

2010-04-13T12:02:00.000-07:00

It's amazing that we're filled with nerves that can't directly provide us experience. When your stomach growls, it's because your autonomic nervous system is sending waves of contraction down your small intestine to clean out any food material that remains. But even though it's your own intestine, you have no power to start or stop this activity, as you may have discovered to your chagrin in a conference room at one point; you "find out" about your own organs' activity only indirectly, by hearing them as if they're coming from someone else, or feeling it incidentally in consciousness-impinging somatosensors on adjacent muscle or skin. This becomes even stranger when you ponder that we have more autonomic motor neurons than we have consciousness-impinging somatasensors. And yet, somehow, this mass of neurons certainly doesn't seem to be conscious. Why not?

I haven't seen any philosophical explorations of the nature of consciousness in terms of the ANS, but it may be profitable to ask what the autonomic nervous system lacks that the central nervous system has. Clearly a large network of neurons is necessary but not sufficient.

The question is not just why we can't consciously form migrating motor complexes in our intestines. They're connected to the wrong part of the brain for that, and there is no instance of smooth muscle which is under voluntary control. (If you can voluntarily move a muscle, it's striated; most of the rest are smooth, with the notable halfway exception of your heart.) As a speculative aside, smooth muscle is structured in a seemingly jumbled way relative to the machine-like geometry of striated muscle, but I wonder if this says more about the way we perceive patterns spatially and temporally than it does about the respective complexity of the tissues. That is, our space and time perception has developed for obvious reasons on the same scale as the voluntary movement of our bodies - of our voluntary nervous system. But the world sometimes becomes alien and even incomprehensible when we look at satellite images or super slow-mo videos; maybe in a real and objective sense there is a logic to the organization of smooth muscle but our pattern recognition filter is not designed to see it. After all, it took until the 17th century for someone to think of integrating information into a graph; there are many accurate ways to represent data coming in from the world, even if our consciousness doesn't automatically tie stimuli together that way.

Birds are another interesting problem. Where the ANS is missing a function (consciousness), birds are missing a structure, but still have the function. Even if they aren't conscious, birds are certainly intelligent, yet they have only a very thin cerebral cortex. Learning in birds occurs in the Wulst, within the corpus striatum. The cognate structure in mammals are the basal ganglia, which are islands of gray matter near the bottom side of the brain, surrounded by white matter. In mammals, they do have roles in learning and decision-making (especially the caudate nucleus and controversially the subthalamic nucleus, respectively) but they are certainly not sufficient. Why is the corpus striatum in birds adequate for learning? What design features does it share or how does it differ from the cognate structures as well as the cortex in mammals?

Semantic Reasoning, and the Spectrum from Heuristics to Delusions

2010-04-10T09:32:00.001-07:00

To what extent are heuristics (especially confirmation bias) just milder forms of delusions? How can we distinguish the two, how can we measure them, and how can we (or should we) treat them?

Delusions are fascinating in that someone with delusions has exactly the same sense input that the rest of us do. Unlike a schizophrenic who hears voices that no one else does, or someone who's taken LSD and sees lights and shapes and animals, a delusional person doesn't see or hear anything different. What he does is take the same sense experience the rest of us have, and interpret it differently. He might have heard the same group of schoolgirls laughing on the subway that you or I do, but where you or I are merely annoyed, the delusional person knows that the schoolgirls are laughing at him, because they're part of the conspiracy. A delusional person engages in top-down thinking, organizing their experience of the world around pre-existing beliefs. Psychiatrists commonly state that delusions are notoriously difficult to treat. You can give a full-on hallucinating schizophrenic medicines that will improve her positive symptoms, but there is no drug available that can dislodge a specific belief that doesn't accord with reality.

In fact there is a spectrum of false beliefs. On one end, we have flawed human cognitive shortcuts (heuristics) like confirmation bias, leading to small and often temporarily held, utterly inconsequential false beliefs. I guarantee that you have such quick-and-dirty false beliefs every day of your life, as do I, as does every human who has ever lived, but they're temporary and small and if they run head-first into information that doesn't seem to fit, we throw them out without noticing and adopt a new belief.

But from there we move on to the realm over-attached ideas, and from there to what most of us (except the delusional) would see as full-on delusions. At first it might seem that a behavioral definition would be the quickest way to measure this spectrum, but there are plenty of people with delusions who can hold down a job and keep the lights on without annoying the neighbors too much; but where and how to draw lines is not an academic question. Psychiatrists have to decide who needs treatment and who doesn't. Let's say your uncle insists that the Apollo moon landings were a hoax. How is this affecting his life? He makes coworkers roll their eyes at lunch and that's about it? Probably doesn't need treatment. On the other hand, imagine you go home and your mother tells you that the neighbors are spying on her and bugging her house and even sent people to follow her on her vacation to Tahiti; she becomes quite agitated when you ask her for evidence, and she insists soon she'll be forced to do something about it. You probably do want her to see somebody about this. And in addition to having a yardstick for what caretakers should do about delusional beliefs, there is the extremely interesting question of why in some people, the gain on the pattern recognition filter seems to be set too high, and they slide down the far side of the distribution from heuristics into delusion.

Keeping in mind that although it would be difficult to operationalize the following approach ethically, we might be able to get a quantitative answer for how severe the heuristic/false belief/delusion is based on how much risk they're willing to take for it (how it affects their decisions); that is, on what confidence they place in the belief when there are consequences, and how much suffering they're willing to endure for it. That means measuring adherence to delusions in the face of negative reinforcement (or missed rewards). That is to say - would the delusional person make a large bet on their beliefs, with generous odds for their opponent? (If they believe it's clearly true, why not give good odds to the opponent(s), to draw in more suckers?) Would they plan a legal strategy or medical procedure based on this belief? Of course, people do make these kinds of decisions based on false beliefs all the time, which shows the extent to which they take them seriously.

There is also a kind of natural selection argument to be made for long- and strongly-held false beliefs. That is, those false beliefs are most likely to survive over time which are attached to behaviors that keep them from coming into contact with clearly opposed reality; you wouldn't have a false belief for long if the belief didn't have these defense strategies. Consequently, delusional people often find ways to avoid entering into arrangements that directly subject the belief to scrutiny (for example, these very sorts of bets or experiments; the contorted explanations of why they won't enter these agreements are a dead give-away). This keeps us from using the previous approach to measure delusional strength, but then possibly the intensity of the protective behavior could be measured. Phobias are similar in that there are also elaborate recursive defenses erected around them; for instance, not only will a severe butterfly-phobic person refuse to talk about butterflies, she will also refuse to talk about having a phobia of butterflies, and refuse to talk about the fact that she won't talk about the phobia, etc. Operationalizing this approach ethically in the laboratory or clinic remains a problem, but people do the experiment on themselves voluntarily. People do in fact risk and lose their health, livelihood or life savings on delusional pursuits; this is why they are treated.

So far I've discussed false beliefs on a spectrum of apophenia, the imposition of patterns on information when it isn't justified, from minor heuristic mistakes to full-on schizoaffective delusions. Humans have developed the unique skill of semantic reasoning, a neat trick that allows us to glean more information from the world than just what our direct senses provide. The unique problem that comes with that skill is that we can make mistakes in those chains of non-sensory association but remain unaware of them.

It bears emphasis that apophenia is a basic activity of human cognition - we face the world with a set of pre-existing ideas, and only very rarely do we independently form a coherent new concept to explain what we've encountered. This is hard. The overwhelming vast majority or our concepts, even for the most original thinkers among us, are taught to us through language by other humans. Although apophenia implies no requirement for the imposed pattern to be pre-existing, in practice, people don't constantly impose brand new (unjustified) patterns on noise but rather filter everything through a top-down principle that's already there; confirmation bias is therefore a special case, although the most common form, of apophenia.

To see semantic reasoning in a fossilized, easily studied form that shows confirmation bias in spades, try analyzing the rhetorical structure of the arguments you hear over the course of a day (I'm not talking about Aristotle, I mean listening to people at work or in front of you at the grocery store). Stephen Toulmin took an inductive approach to rhetoric and showed that, when making arguments, what humans really do (almost always) is start with the end in mind, and get across to it from their premises on whatever rickety and incoherent rhetorical bridge they can put together. This is how humans actually make arguments, even if it's not an effective way to get at the truth. While it's true that humans do sometimes begin a chain of semantic reasoning without a conclusion in mind, this is a vanishingly small fraction of human semantic reasoning, even in people with good critical thinking skills who are paid to do it. (Critical thinking and self-criticism can be thought of as a form of recursive semantic reasoning that we've been forced to develop to avoid going off the rails constantly.)

It's exactly this semantic reasoning ability that begins to overtake sensory input the further we get toward the delusional end of the spectrum. To test this model, it may be productive to ask:

1) Whether individuals who grow up speaking more than one language are any less likely to become delusional (controlling for intelligence). Since concepts and definitions of words are not exactly analogous between languages, if delusions result from a flawed semantic reasoning process, the cognitive coexistence of 2 or more languages may offset errors.

2) Whether otherwise functional delusional individuals have more difficulty modeling false beliefs in others. This brings up the question of the overlap between delusion and autism, since one of the principal features of autism is the inability to model others' beliefs, especially false ones.

3) Whether individuals with language deficits are less likely to suffer from delusions.

4) Whether delusions and hallucinations are really two entirely different phenomena with different pathologies; this model predicts that delusions and hallucinations are two different phenomena and that there shouldn't be much overlap between the two (no spectrum). After all, if you believe someone is screaming in your ear that the house is on fire, the rational thing to do is run out of the house. Hallucinating people can sometimes be said to react rationally to false stimuli, as opposed to delusional individuals, who are doing the converse.

5) Lysosomal storage diseases have controversially been argued to be selected for by heterozygote advantage (increased semantic reasoning in heterozygotes). If this is ever established by direct testing of heterozygotes, it would be productive to see if increased semantic reasoning ability has an affect on risk of developing delusional beliefs.

Other Characteristics of Delusions

1. Evangelism. In addition to apophenia, false beliefs that we would normally categorize as delusions often have a compulsively evangelical component. That is, your neighbor insists that the town is poisoning the water supply, and what's wrong with you that you can't see it!? You must believe it! In fact this evangelism extends right up to and through serious consequences, like loss of jobs or relationships. How does this differ from non-delusional false beliefs? Let's pick a belief of mine that I (of course) think is true, but which large numbers of people think is false, that being my position on property dualism. However, if tomorrow I awoke to find that this had somehow become an offensive taboo topic, I would decrease my discussion of it (even if as an oppressed minority I would start working behind the scenes to make it acceptable again). As it is now, most people just don't care, so I generally don't bring it up other than with neuroscience students, philosophically-minded acquaintances, or on my blog.

Most people do hold beliefs which a) are not "mainstream", b) about which we wonder "what's wrong with people" that they don't agree, and c) that we do "evangelize" about - but we can shut up when we need to avoid boring or frightening people, or jeopardizing our careers. Delusional people often have trouble with this restraint, even if the subject of their delusion is something with no immediate threat to their or anyone's safety. (The topic of all humans' epistemic intolerance, far out of proportion to any threat to personal health and safety, is certainly a fertile topic.)

2. Social Context. Part of the offical psychiatric definition of delusion contains, strangely enough, a reference to the culture of the people putatively experiencing the delusion. That is, it's not a delusion if everybody where you live believes it. Suffice it to say, that's strange. While I don't intend the post to be an argument against religion, not to address the culture-specific nature of this defintion is to ignore the elephant in the room when we talk about delusional beliefs. There are some delusions that individuals develop all on their own, and these "stick out", because they're not culture-bound. Then there are delusional beliefs that are taught. Some of these exist in isolation ("black cats crossing the street in front of you cause bad luck") and some of them are deliberately reinforced by institutions and exist in complexes with other beliefs ("bad things that happen to you now are the result of bad things you did to others in a previous life"). Without arguing that all religion is delusional, believers and non-believers both can agree that some beliefs of some religions certainly are delusional, and while it's sometimes useful to be politically correct about it, no, their kids really recover from an illness because they set some photographs in front of a statue.

To illustrate the silliness of it, this means that someone in the U.S. who induced labor early to avoid the bad luck of delivering a child on 6/6/06 is not delusional (because lots of other Americans believe that number is bad, and lots of people actually did this!) but someone in China who did the same thing would be. It's also worth asking what this definition says about people who have extreme non-mainstream beliefs for which they can produce evidence. Was Galileo delusional? It seems a very short step from this to "the majority is always sane".

Of course there's a difference between a psychological definition of a belief as "not [officially] delusional" vs. recognizing it as true. We can recognize the pragmatic aspect of clinical practice and even a need for some political correctness to avoid seeming threatening to the public; to show up at Fatima and start prescribing antipsychotics would probably not get very far, and these people are often functional as part of a large group that shares the delusion. But it still seems prudent to remove this part of the definition of delusional, and make it a practice to categorize some people as "delusional but functional within a culture complex, therefore inadvisable to treat". Naive about the practice of medicine though I still am, at this point in my young career, that seems like this would be an honest, appropriate and accurate thing to write in a chart.

3. Self-Reference and Emotional Content. Has anyone ever delusionally believed that a casual acquaintance is being pursued by the CIA (as opposed to the CIA pursuing the delusional person him or herself?) Or has anyone ever become obsessed with spreading the gospel that Kenmore refrigerators in 1999 used 1 1/4" tubing instead of 1 1/2" (and what's wrong with everybody else that they don't know this?!?) I doubt that these kinds of delusions are common; passionately-held beliefs require some degree of inherent excitability. Threats to personal or public safety, or paradigm-shifting facts about the country or our history seem to make frequent appearances as delusions. One telling exception is that there is a class of people probably more in the over-attached idea category rather than fully delusional who we call "crackpots". These are the people who claim to be able to show you that they've disproved relativity, or the Basque language is a form of alien mathematics. Their appeals are to a narrow and obscure slice of the public but tellingly, they focus on the high status people in that field, from whom they demand recognition. Pascal Boyer has an excellent piece on crackpots; similar status-seeking behavior can be found right at UCSD, as it turns out.

The idea that delusions require emotional content is consistent with their position as the organizing principle of semantic reasoning in delusional people, and with what we know about the effects of traumatic experiences on brain architecture and cognition. Building on work by Tsien, Josselyn, and McGaugh, Kindt et al showed that human fear behaviors connected to a learned stimulus can be erased with the off-label use of propoanolol, a beta adrenergic antagonist that's already on the market. If delusions are organized in a similar way, perhaps administration of propranolol during behaviors driven by delusions could have a similar benefit.

4. The Over-Extension of Agency Onto the World at Large. To delusional patients, the world is often purposefully organized to some purpose, either very positive or very sinister - otherwise the delusion wouldn't have a strong emotional component. What this means is that everywhere the world itself watches them (with bugs, cameras, and secret agents, or with a powerful protective charm that makes them successful and keeps them from getting hurt in bad situations.) These people's agency detectors are over-active.

It's interesting that the dissociative anesthetics are currently considered the best pharmacologic model of schizophrenia and that one of the toxicities of chronic ketamine use is over-active agency detection (for a good example, see the delusions of John Lilly, M.D., of the Solid State Intelligence). While serotonin agonism has been mostly abandoned as a pharmacologic model to study schizophrenia, it should be noted that users of the HT2A agonist DMT report as a residual toxicity a sense of being watched by a disembodied mind. It's worth developing a way to measure this symptom and tracking the effect of serotonin antagonists on this symptom in delusional patients. Again returning to cases of autistics with delusions, it may also be instructive to see if delusional autistics experience these symptoms at the same rate as non-autistic delusional patients, since autistics are known for have an under-active agency detector.

CONCLUSION

As animals that make sense of the world not just through their senses but through chains of semantic reasoning, all humans commit confirmation bias errors that lead to false beliefs. For most of us, these errors are transient, do not dramatically affect our behavior, and can eventually be corrected by further information. For some humans, semantic organization or perception takes on too large a role. Cognition becomes predominantly top-down, and these humans become more heavily invested in false beliefs, to the point where harm to the health or property of themselves or others can occur. People at this end of the spectrum are delusional, and in addition to apophenia their false beliefs have other characteristics. These beliefs become central organizing principles of their cognition in part because they are strongly associated with highly emotional behaviors. Sometimes, these beliefs are reinforced socially by others who share them; the current official definition of delusions is somewhat disturbing with respect to this topic.

We can use willingness to adhere to the delusion in the face of financial or physical harm as a measure of severity. Ultimately, there must be a physical correlate in the brain for persistent, harmful, false beliefs, but efforts to detect or image them (should they ever seem feasible to explore) should be focused on treatment.

For fear memories in general we already have some indication of the physical correlates of the fear-association, as well as an experimentally verified way to erase memory-associated fear behaviors. This same therapy may be productive for delusions. It would certainly have fewer side effects than current antipsychotics. It is also worth asking whether there is a genetic contribution that predisposes individuals to delusion.

Transporters, Zombie Neurons, and the Hard Problem of Consciousness

2010-04-09T23:39:00.000-07:00

Most philosophical materialists who investigate the hard problem of consciousness accept that consciousness is associated with matter being arranged within certain bounds: a central nervous system with inputs. Change that arrangement, and you will change or destroy consciousness.

This leads to thought experiments like the transporter problem. If a device exists which can break down the atoms that compose your body and send them somewhere else and recompose them in the same form, many (most?) thought experimenters would argue that the person produced at the other end is not you. This is my position; you're dead the moment that you get broken down. Certainly the person at the other end will step out with all your memories right up until the moment of breakdown and say "Was I ever silly to have doubted that!" - but you are dead. If this seems unclear, imagine several possibilities.

First is that the transporter malfunctions and sends a copy of you (same atoms or not) to the other destination, without breaking you down in the first place. Are you suddenly seeing out of four pairs of eyes simultaneously from both destinations? Another way to imagine it is if it were very low-tech: you're broken down into atoms, and someone records all the information about the arrangement of the atoms in your body with paper and pencil. This record is then sent by Pony Express from St. Louis to San Francisco, in which city chemists laboriously reconstruct "you" from the formula. Again, assuming the technology to perform such a feat chemically ever exists, certainly the person who wakes could honestly say "Wow, the last thing I remember was being broken down in St. Louis, and here I am in San Francisco two years later!" First, the (real in this case) continuity of memory cannot itself be an argument for the continuance of subjective experience - if we load up someone else with your memories, does that make them you? If we load up someone with false memories, does that mean the false life thereby represented actually happened, and the person in those memories is now reified? Certainly in the Pony Express transporter, a person will wake up in San Francisco with your memory, who thinks s/he is you, and is physically identical - but you won't ever wake up again once they take you apart in St. Louis.

Would it make a difference if the chemists in St. Louis send not just the instructions, but vials of the actual atoms of carbon and nitrogen and oxygen they got from your tissues? Self-evidently not, and atoms are equivalent anyway (unless we're going to suppose some elan vital or special consciousness juice for them. Which we're not.)

It's also worth comparing your post-disassembly fate, as a conscious human, to that of Hernan Cortez's ship. He had his men disassemble the ship at the shore of the Gulf of Mexico and carry it inland and uphill hundreds of miles, to be reassembled it in Lake Texcoco to attack the then-island capital of Mexico (yes, this is really what they did!) There was a ship in the Gulf; then a bunch of wood and nails and rope, but no ship getting carried up from the lowlands and back down to Tenochtitlan; and then again a ship in the lake. Where was the ship during the trip? A ship is just a certain arrangement of elements - so it was nowhere. The crucial difference is that a ship has no experience; there is nothing it is like to be a ship, so there is no property to be lost in the transport, regardless of whether they send the original wood and rope or just a set of instructions so the conquistadors can build another ship when they get to the lake.

The problem with the transporter thought experiment is this. If our continued experience is a product of the continued functioning of a specific material arrangement, how can any of us exist for more than a split second? Every second of every day some of your brain cells are dying, some of them are building new connections, molecules are being delivered or carried away by the cerebral vasculature - that arrangement is constantly changing. And yet, of course, despite each specific material arrangement of the brain being constantly destroyed moment-to-moment, we seem to be continuously conscious.

There are several possible ways out of this conundrum.

- The transporter-kills-the-old-you position is incorrect.

- Our seeming to be continuously conscious is an illusion. Each of "us" exists as a conscious entity only for mere fractions of a second, but we cannot tell, because we still have the entire memory of the last incarnation, and of course we're not conscious of our own immediate extinction.

- There's a limit on how much rearrangement can occur to your brain and allow continuity of experience. On one hand, these sorts of absolute differences in kind (rather than spectra of degree) are usually suspect. On the other hand there clearly are limits to the changes that can occur to tissue and allow persistence of the self.

The last option is the most attractive but it suffers from some of the same problems as does property dualism (a more respectable name for panpsychism). For example, if your brain as it is in this nanosecond is conscious, presumably that doesn't preclude your brain as it is in this nanosecond minus exactly one neuron in the dorsolateral prefrontal cortex from simultaneously being conscious (and so on in some enormous factorial function that gives all the possible combinations therein). If this is true and each arrangement is conscious discretely, either a huge number of conscious entities exists co-dominantly within any one brain, or the vast number of human consciousnesses are locked away, looking on from inside as one lucky combination of cells interacts with the outside world.

Asking these kinds of questions allows the problem of philosophical zombies to invade one's own skull. There is no way for any of us to determine that any other living thing has subjective experience of the world. As a thought experiment, imagine wiring your own brain up to a friend's, from whom you would receive all of their impressions of the world (a la Being John Malkovich). You would find that you were certainly having an experience not only of your friend's senses but of thoughts, memories, reactions to those subjective experiences, and so on - but the issue is that again, you have no way of knowing if you're "contaminating" your possibly-zombie friend's brain with your subjective awareness, if anybody was home in the first place or if you're just experiencing dead inputs and your own consciousness is imbuing those inputs with subjective experience. You could ask the same question of an inert, 100% certainly-unconscious piece of matter like an eyeball. On its own, and eyeball is not conscious. Wired into your brain, it is providing the raw stimulus for a subjective experience of vision, but only that - the eye itself cannot be the source of experience, only a source of information, if the two have no overlap. Given that on its own the eye is just a photochemical transducer, we might even reasonably ask why we would consider the eye to be the generator of experience, and not the flowers the light is reflecting off of, or the sun that's producing the light in the first place.

We can ask the same question about wiring up to your friend's brain or a new eyeball as we can with new neurons. Imagine the frightening event that you have a severe stroke, and lose large portions of your frontal lobes. Now also imagine that after an intensive surgery, your brain is repaired with frontal lobe sections from an organ donor. The same argument applies; is the new lobe capable of experience on its own, or did your remaining brain "contaminate" what was previously a zombie lobe? (And does consciousness always win, or might a zombie lobe overpower the conscious lobe into zombiedom? If a question seems silly, it probably is; such is usually the case when we dig deeply into the assumptions that make us accept differences of kind in nature.) More realistically - you're conscious now, yet your consciousness is built out of parts that are certainly not conscious (or at the very least much less conscious) than you are. And that's not all - "you" were not always capable of consciousness and in fact, the arrangement that is you was not even always capable of consciousness. There was a time when you were an embryo and did not even have neurons, much less a brain.

This has become a reductio ad absurdum. The question of philosophical zombies is meant to question to basic assumption of materialist accounts of consciousness, that a certain kind of arrangement of matter is what creates (or enhances) consciousness, and if two identical constructed identities differed in their degree of consciousness, the materialist account would fall apart. But once we assume that there is even one consciousness entity, then to assume that there could be zombies, or even that a part of the world is unable to provide subjective experience, we must make arbitrary distinctions outside world and central nervous system - while forgetting that the CNS is made up of discrete combinations of elements which in isolation are certainly not conscious, and which themselves originated from an experienceless state. Why assume another human brain that you're wired to, and which is now a causal factor in your experience, is a unique topic for the question of zombiehood, and your contamination of it with your "core" of consciousness? By having an experience of a flower, are you not contaminating the flower with your consciousness in exactly the same way? If it was not capable of interacting with you in an experiential way to begin with, even if it's depending on your eyes and brain to complete the experiential equation, you would not be able to have a conscious experience of it. Extended most generally, all information must be able to provide experience.

This is one approach to solve the problem of second-to-second changes or 1-cell different combination differences causing discrete consciousnesses. Any combination or arrangement whose elements have the basic requirements for consciousness is conscious (there can be no zombies then). Although consciousness can be profoundly reduced as with transporter decompiling, as long as the core basic requirements of the arrangement of entities is met, there will be continuous unified experience. This is also consistent with the panpsychist or property-dualist position advocated by Chalmers, that experience is a basic property of reality, and like gravity, consciousness changes its quality in response to aspects of matter around it.

The Tactile Binding Problem and Literacy as Synesthesia

2010-04-08T07:30:00.001-07:00

The term "binding problem" is used in several ways, which as is often a problem in a convergence discipline that is also "neat", muddies the waters. The clearest meaning is the limited one, where investigators are asking questions about how we can perceive a specific coherent stimulus with specific multiple properties where those properties are received and processed by discrete channels; color and shape in visual perception of an object is a common arena for these questions. In other words, when you look at a green bottle on a black table, you don't have to decide whether the bottle or the table is green or black (or whether the green thing is the bottle-shaped surface or the flat square surface). In fact you can't not see the bottle-shaped surface as green; you have no choice in the matter, since the two properties are combined before they enter your experience.

Sometimes people also use the term binding problem in a more general sense, of how all these stimuli are combined to form our full coherent conscious experience of the world. While a worthy goal, it's easier and more productive at this point to ask questions about the limited definition of the first sense of the term. Read about or click through to one such recent productive investigation here.

Another binding problem that I've not seen investigated is the tactile binding problem. Areas of skin on our torsos are innervated by discrete nerves emanating from specific positions between our thoracic vertebrae - yet to learn this, humans needed to study anatomy, rather than perform introspection on our experience. When something touches your chest and moves down to your navel it's traversing 10 separate nerves, but as with visual binding, there's no sense of "transfer" between channels; it's completely continuous. Why? Is the answer the same kind of answer for visual property binding pairs? Maybe that's another potential angle of investigation; maybe easier.

Note that there are some forms of possible, non-automatic pattern recognition (not "mandatory" pre-conscious pairs) that are highly semantic. That is, I go for a walk in the canyon behind my house, and if I'm paying attention, I see tracks in the dry dirt; if I'm paying more attention, I can differentiate them as coyotes rather than domestic dogs; and if I'm really concentrating I can determine that there were two of them, they were there about dawn, were chasing a rabbit, and ran down into the creekbed after it. Unlike sensory binding it would be easy for this process to be derailed. That is, imagine that I like bunny rabbits and find it unpleasant to think about their being devoured. If I see all the tracks and begin to suspect that Peter Cottontail met an untimely end on this very trail I could choose to distract myself from these highly voluntary semantic pattern-recognition efforts, and never consciously realize what happened. But if I come upon the coyotes at the start of their meal, then, no matter how much I might want to avoid it, I have no free will in the matter; my brain will bind "red" and "bunny rabbit shape" and I will be conscious of it.

Of course, my semantic reasoning about these marks on the ground could have been all wrong, and in fact this is much, much more likely than when I preconsciously integrate "bottle-shaped" and "green" or "bunny rabbit-shaped" and "red". Semantic reasoning allows us to have false beliefs, but even the integration of direct sensory input is not without glitches; optical illusions do occur. Both means of perceptions involve integration of discretely sensed information, it's just that one of those integrations is occurring voluntarily, consciously, and semantically.

What's more interesting (and the subject of another post) is that semantic learning that's so well-conditioned it is also automatic and pre-conscious, for example writing to literate people. You can't look at an "A" shape without thinking of the letter, even if it's a natural rock formation that humans have never touched. You can't see the word "cat" without thinking of the animal. (If you disagree, email me with your perfect Stroop test score.) There are various forms of synesthesia, many of them having to do with graphemes, and I submit that literacy is a form of conditioned grapheme-sememe synesthesia that only seems non-miraculous because we've been doing it for a few millennia. (A sememe is just a unit of semantic meaning.) Connections between various forms of synesthesia and reading/writing ability are therefore interesting, and anecdotally there is a positive association between dyslexia and synesthesia.

I Need Mie Gakure! Where Is It!?!?

2010-04-08T07:20:00.000-07:00

Two things about Mie Gakure: 1) It appears to be fourth dimensional Crystal Castles. 2) I need it now. It was mentioned in XKCD and I'm not the only person freaking out about it; article with video demo here. I don't know whether it will help in discussions of free will but, more importantly, it will be cool.

I wonder if this was the first product placement in XKCD?

Piagetian Stages and Animate-Inanimate Distinctions in Language

2010-04-07T09:48:00.000-07:00

Animate-inanimate distinction distinction is one of the more strongly recurring parameters in languages. The distinction has varying levels of importance and morphological encodedness in languages, from purely semantic as in English (the tell-tale is whether we assign gender) to more complex grammatical structures. Inuit languages even have a fourth person required when there is action between an animate third person agent and an inanimate agent ("He moved the boat"). In many languages, inanimate nouns cannot be the agents of actions against passive patients (you cannot say "The rock hit him", you must use another construction analogous to "He was hit by the rock").

Again we should take advantage of differences in neurology between humans, including those associated with pathology as well as those which we see in the normal range of development. Piaget noted that from the beginning of language production until about age 6, children indiscriminately assign animacy to inanimate objects: the sun shines because it's "happy", the toilet "wants" to suck them in. If we're honest, adults resort to this kind of thinking as a coping strategy when the cognition gets tough; medical students frequently hear during lectures that sodium "wants" to flow into a neuron .

But sodium's desires are a consciously used linguistic conceit, and we would expect that a neurochemistry lecture in Inuit would unmysteriously use animate rules for sodium until switching back after the didactic task is finished. Inuit kids talking about toilets sucking them in, and everything else, are unable to slice the world into these distinctions at all. The animate-inanimate mistakes made by children speaking these of languages at this age may therefore be instructive in investigations of human cognition and the physical correlates of the animate-inanimate distinction.

Intelligence, Language and Behavior in AIs and Animals

2010-04-06T22:50:00.000-07:00

If someone came to me with a machine that could survive on its own for years in the canyon behind my house, not only finding its way around but scavenging fuel and meeting others of its kind to make more of itself so that there was sustainably and indefinitely a population of these machines back there in the brush, I would be damn impressed. I would even be prepared to call this invention "intelligent". Of course there really are such machines down in the canyon already; they're called coyotes, and they're pretty clever, but they aren't about to pass any Turing tests.

Cognitive philosophy discussions are often confused by equating "language" with "intelligence", or even assuming language is a good quick-and-dirty proxy indicator. Turing himself stressed the dirtiness of the measure at the beginning of the article where he introduced the test and didn't argue that a command of language necessarily required the commander to be thinking and/or conscious. Teaching a box to repeat superficial pleasantries for a finite duration, without that language relating to spontaneous behavior, seems like a fairly superfluous parlor trick and one which doesn't have much to say about intelligence. It's worth asking whether programmers working in a more highly inflected language like Russian are as impressed with this goal; if not, maybe they realize populating a structure with terms whose semantic content doesn't violate category expectations too badly doesn't prove much. Great, you wrote a program to tack case endings on the thousand most commonly used nouns, and some Markov chain rules to decide when to use them!

It seems clear that in the natural world some form of consciousness and spontaneous problem-solving behavior preceded language. There are animals from several taxa with excellent problem-solving skills (other primates, bears which arguably even have memes, crows, even octopuses) but without language. Leaving aside the hard problem of consciousness, we can measure behavior.

It's perhaps understandable that we're approaching this question bass-ackwards since instead of the natural world where language developed very late on top of and in context with self-replication capabilities, our toolkit is a class of entities which began as symbolic, syntactic rule-followers. But for more fruitful attempts at AI, we would do better to focus on building generalized problem-solvers and forget about chatbots. I suspect Turing would agree. That approach is the most likely one to effectively make the question of whether a machine can think seem as moot as whether a submarine can swim.

A Sketch of a Neuro-Linguistic Theory

2010-04-06T18:30:00.000-07:00

Below is a brief sketch of a neuro-structural theory of language with a few supporting comments. following that is an outline of a program for exploring questions in historical linguistics. If similar work exists or you have thoughts (critical or otherwise) I would greatly appreciate hearing them in the comments.

1. Distinctions occurring universally or re-developing frequently in human language will have physically detectable neural correlates. They should be further investigated by pharmacological disruption of subsystems or review of patients with neurological deficits.

2. The basic unit of human language is the noun. All phrases are noun phrases. It is difficult or impossible to derive coherent information from isolated non-nouns, except for direct sense impressions ("green", "loud"). This has strong implications for cognition.

2-1. Chemical and electromagnetic imaging should eventually reveal nuclei or
networks of cells corresponding to specific nouns that when activated by an
utterance, activate earlier than other words in an utterance, regardless of
language word order. Children learning a language produce nouns first.

2-2. While nouns are often grouped into genders or other categories based on
some attributes, these are invariably irregular, and it is better to
use neutral terms like as noun class. Nonetheless frequently re-occurring
categories will have some neural correlate (for example, animate/inanimate
oppositions).

2-3. Possible problem for the theory: supposedly the Athabaskan language Hupa
of Northern California has a very limited number of nouns (a few hundred)
and the language is somehow constituted primarily by verbs [reference to
come]. This is easily the strangest thing I have ever heard about a
language and is reminiscent of Berkeley and Borges [reference to come].
However, I believe there are no native speakers left, I've not yet seen the
primary source and facts I've been able to gather are scanty. My hunch is
that either the primary source was a century-ago grad student who got a
little excited or that the primary source has been misinterpreted. However,
if this grammar is accurate, my noun-based theory is undone unless there are
somehow basic neurological differences between the Hupa and the rest of
us. Further militating against such radical innovations are the fact that
no other Athabaskan languages demonstrate such alienness, even those also
located on the Pacific coast like Port Orford and Tlaskanai [reference to
come.] This is a critical point of analysis for the theory and if any
speakers do exist, it would still be worth doing neural and genetic
investigations to see how they differ.

3. There are primary modifiers that directly modify nouns, in traditional grammar referred to as verbs and adjectives.

3-1. Primary modifiers encode information relating to the noun they modify
(number, noun class, case, time and intention). In many languages time is
encoded on adjectives, confusing to speakers of Western Indo-European
languages (e.g., Japanese, Mohawk).

3-2. Beyond their morphosyntax, the only distinction within the category of
first order modifiers is semantic, i.e.g, whether the modifier can mediate a
relationship or property between nouns. If so, these are called transitive
first order modifiers. If not, these are intransitive first order
modifiers. In English, adjectives are intranstive primary modifiers that
cannot be encoded with time information.

3-3. Even in languages like English or Spanish where there is a class of primary
modifiers not thought of as encoding time, there is a high degree of
interchangeability to the point where the adjective-verb distinction is
unclear. In Western Indo-European languages these are participles. It is
not possible to distinguish whether the last word of "She is finished" is an
adjective or verb because the categories are unnecessary.

3-4. Reflexivity is a form of ergativity; in languages where both exist like
Greenlandic, ergative blocks the reflexive morpheme. [reference to follow]
If there is a "native state" of languages with respect to ergative-
absolutive or nominative-accusative alignment, it is that all languages are
actually stative-active and contain both systems but where they are marked,
one is much better developed than the other. The alignment system is always
an extension of the animate-inanimate system.

3-5. Problem for theory worth investigating: relationship and storage of
abstract terms in terms of senses. To borrow and abuse terminology from
analytic philosophy, if we understand "cat" as the primary "anayltic"
element and primary modifiers are parasitic on the noun's concrete
qualities, then in neurological terms, "cat" cannot merely be a network of
primary modifiers - or they would be the elements. Note again that for any
materialist theory of language there must be some physical collection of cells in some
state in our brains that produces the semantic experience of "cat"; how it
is arranged and constituted relative to these other terms is the question.

4. Languages have secondary modifiers, in English called adverbs, which can modify primary modifiers. Their marginal importance is highlighted by their having little or no morphology, fewer or no rules about order in the sentence, and being often oddly affixed with cognition- related terms ("-mente" in Spanish, "-wise" in English).

5. There are non-content logical operators that mediate relationships between nouns. They are especially incoherent in isolation and are in fact always particles, even in languages that are not considered agglutinating.

5-1. There are two classes of non-content logic operators, those which can be
classified as those which give information about relationships between nouns
(in English, prepositions and conjunctions), and those which do not (in
English, articles; in Austronesian, focus markers, but they are actually the
same word category). Logic operators which do not provide information about
relationships between nouns often provide information about the importance a
speaker places on a noun.

5-2. Logic operators are often marked to agree with the nouns they modify.

5-3. Belying their close relationship, logic operators from the two classes
frequently merge; this could be better support if this is shown to
statistically occur over time more often than their ancestor words' use
together and their phonology would otherwise encourage.

5-4. Like other non-noun, non-primary-sense-datum words, these words are also
meaningless unless they are attached to a noun. In that sense they are like
particles, although they can have active morphology.

5-5. Languages with rich noun morphosyntax (particularly for grammatical role,
i.e. case) will have a far lower use of non-logic operators. To wit, the
parallel and independent developments of increased use of prepositions and
the institutionalization of articles in Western Indo-European languages
(Old English to modern English; Latin to Romance).

5-6. A physical correlate of operators is found in EEG studies. Normal English-
speaking subjects show a smaller ERP on reading prepositions than on reading
nouns, presumably because greater resources are required to recall the nouns
which contains extensive learned, networked sensory content. This
difference is not evident in schizophrenic English-speakers who must expend
the same electrical effort to recall prepositions as nouns. [Reference to
be inserted.] Notably, schizophrenics are grammatically intact but
semantically deficient, in terms of logical relationships of words, word
choice, focus and direction of discourse.

5-7. Language-deprived individuals retain an ability to produce discourse with
adequate logical word relationships, word choice, focus, and direction;
however they are persistently unable to learn to use logic operators in the
correct orientation to nouns, sometimes using them adjacent to primary
modifiers ("the ran"). [reference to follow] EEG studies are predicted to
show a normal lower-than-nouns recall of operator words (but this study has
yet to be done).

5-8. Schizophrenic speakers of languages with rich focus and topic-marking
systems are excellent cases for this theory and others which seek to
investigate the relationship between language and cognition, because
logical relationships in the speaker's cognition are more exposed. Washoe
has a famously complex topic-marking system [reference to follow] but
likely has no remaining native speakers. Tagalog or other Austronesian
languages may be good alternative candidates.

5-9. It is logical operators that allow recursion. Operators can place phrases
in subordination as a primary or secondary modifier to nouns or primary
modifiers respectively, or as equals (we call these operators
conjunctions). Studies of the spontaneous production of recursion in
schizophrenics may be useful.

6. Non-content non-operator terms (exclamations and hand gestures) can be thought of as products of the autonomic nervous system; they can be trained by their utterance does not carry semantic information though they may be rich in social signals.

7. Personal pronouns in this framework are similar to their understanding in other theories. Their repeated re-development in human languages in similar roles and their marking for number, gender, grammatical role, and social status reveals underlying categories in human cognition that must have (eventually) measurable physical correlates in the nervous system.

8. Word order - word order in any individual is the result of inductive learning; i.e., raise a child speaking only English with VSO order, the child will produce VSO English (hypothetically; experiments testing this hypothesis would be informative).

8-1. There are languages that resist classification as having a specific word
order (not just like English where discursive functions change word order;
normally English is SVO but we utter OSV statements for contract - "I
don't like spaghetti, but linguini I like." - and are best described in
terms of statistics, for example Tsimane. [M. Gurven, personal
communication]) This should be troubling to strongly rule-based word
order generativists.

8-2. The current theory predicts only that there will be a general statistical
tendency across human languages for words to occur temporally earlier in
sentences based on how basic they are to cognition. Consequently
noun-before-verb orders will be more frequent, and nouns will more often
than nouns precede first-order modifiers and particles.

8-3. Investigating the relationships between most permitted word-orders is not
necessarily productive (i.e., SOV languages tend to have postpositions not
because of any structural necessity but because there is a plurality of
SOV languages due to the importance of nouns, and more languages have
noun-initial phrases, so statistically we should expect lots of SOV and
postpositional languages; similarly there is little information in a
language like English that has noun before transitive first-order modifier
but noun after most intransitive second-order modifiers). Much more
interesting is arrangements that are universally forbidden. Why are first-order modifiers never in
any language further from the modified noun than logical-operator phrases
acting as first-order modifiers? [Reference by R. Morneau to follow]

Underlying the whole program is that the point of studying language is two-fold: first, to understand human cognition better; and second, to illuminate events in prehistory, which questions can also serve the primary goal. There are historical questions that are interesting for both of these reasons.

Some Investigations With a Novel Historical Linguistics Genetic Approach

A. An approach to determining genetic relationships between languages using phylogenetic methods on morphosyntax rather than phonology as with the comparative method may be fruitful. Morphosyntax must maintain some level of internal consistency and is constrained by neurology, so it necessarily a more conservative element of language and may enable reconstruction of relationships in deeper time than is possible with phonology-based methods, following the call of Nichols and others to focus on critical languages in the hopes that patterns of prehistoric migrations will be illuminated. Once the genetic patterns of well-attested languages have been reproduced by this method, it can be pushed further back for questions as follow.

B. What, if any, are the relationships between the current language families of Eurasia? How do these compare on the large scale to the genetics of the speakers of those families and the timing of the spread of important memes as shown by archaeology?

C. What, if any, are the relationships between the language families of North America? Given the the likelihood that Native Americans are descended from an isolated population of roughly 20,000 that survived in Beringia and began their diaspora near the beginning of the Holocene,[reference to follow] it is likely at the very least that they spoke similar languages at that time, and that deeper connections to northeast Asia exist and could be elucidated.

D. A new approach to the sprachbund problem - can a morphosyntax-based genetic method distinguish between areal (lateral) effects and genetic descent, thus illuminating contacts in prehistory? It's well-known that morphosyntax is the last feature to be borrowed between languages in contact, possibly again because of the need for systemic consistency. After training such a system on the well-attested Balkan sprachbund, it could be applied to investigate possible Uralic contacts with Germanic as the motivation for Germanic's innovations relative to Indo-European, as well as the sprachbund identified in the south Cascades by Delaney.[Reference to follow.]

E. A quantitative approach to model language development over time in the Oceanic branch of Austronesian. The mostly isolated languages of Polynesia can be to linguistics what the Galapagos were to Finches for Darwin. Estimates of population size over time, travel between islands, and internal constrains of the languages' structures can be built into a model that predicts language innovation rate and type.

F. Grammatical simplification of imperial languages. Latin's grammar simplified quickly during the Empire, and the Chinese languages were prefixing fusional languages as recently as twelve centuries ago.[reference to come] Is this a feature of all languages of multiethnic empires, i.e. did pre-classic Nahuatl require more grammatical decisions-per-syllable than the Nahuatl of Moctezuma's day? What is the mechanism (current theory, non-native speakers moving into the polity introducing imperfections through contact via intermarriage and trade).

G. What do the patterns of language evolution over time reveal about human neurology? What can we say about the biological basis of cognition based on the rate of recurrence of certain categories or grammatical rules? Bickerton [reference to come] began the investigation of this question in the context of creoles. With reference to creoles but more abstractly, are there generaly principles of what structural features survive or are innovated when there is a collision between two systems of rules that have some requirement for internal consistency? (e.g. lateral transfer of genes in biology; rule-based productive memes, like music, for example the blues and rock scale in the West which redeveloped pentatonic scales like those used by most humans)?

H. Experimental investigations of the neurologically-mandated structure of language. There are structures in human languages that, while possible and logically consistent, we never see. Attempting some objective measure of complexity, take two groups of subjects and teach each a constructed language (conlang). One group learns a language of that mimics real grammars, the other a conlang that contains never-observed patterns. Use the same phonology and control for complexity; see whether there is a difference in error-free production.

I. Experimental investigations of the impact of grammar rules apart from phonology. Take monolingual speakers. Again teach them conlangs. One conlang has a grammar identical to their own; another has a grammar imitating a real language of equal complexity. See if there are savings, i.e. if speakers more quickly and accurately learn the language whose grammar mimics their own but even though it shares no word roots at all.

J. An interesting and extremely controversial question is whether there are any genetic differences between individuals causing variation in the neurological hardware that the languages are running on. This might easily be true in a trivial sense between individuals; that is, there are genes affecting language use that differ within populations. More interesting but more disturbing is the issue of whether there are language differences in genetically distant populations owing to genetic-based cognitive differences between populations. That is, are there strange twists in Khoi-San or Pygmy languages relative to Indo-European that can be attributed to genetic, rather than cultural isolation? [Reference to come later.] Until recently many scholars put Piraha in this category but a) evidence increasingly suggests the differences in Piraha language usage are culturally-determined and b) we also would be less likely to find a genetic outgroup in a distant spreading zone than in Africa or at least in the Old World [Reference to come later.] This would also be a place to test the lysosomal-storage heterozygote advantage theory of Harpending and Cochrane [reference to come].

Schizophrenia and Heterozygote Advantage

2010-04-06T18:14:00.000-07:00

The classic work on evolutionary medicine is the 1996 volume Why we get sick: the New Science of Darwinian Medicine, by Williams and Nesse. It's not classic enough that I've read it yet, so I may be rehashing some of their arguments. However, on reflection it seems there are four general ways to explain illness.

1) Noise. Entropy is positive; things break, and once you're past the age where your genes have assured their survival into another generation, you're largely expendable. (There are very important wrinkles to this in meme-rich species like us, but the general idea holds.) The idea seems clear enough, until you're explaining to your grandmother who's dying of heart failure that it doesn't matter because her DNA has passed on.

2) Pathogens. They evolve and new ones appear from elsewhere to which organisms have no resistance.

3) Mismatch. Environments can shift rapidly. Mismatch hypothesis was conceived about humans especially, who exist in dramatically different environments from that of our paleolithic ancestors a mere hundred centuries ago, owing almost entirely to physical changes we have made to our own surroundings. (Agriculture, living in cities, reading, mating and dominance patterns, etc.)

4) Heterozygote advantage.

The long and short is that there are a lot of schizophrenia candidate genes and no solid reason to link any of them to specific behaviors or treatment responses; only now are we starting to correlate their response-to-treatment with drugs. The classic case of heterozygote advantage is beta-thalassemia as a form of malaria resistance, but the explanation has since been expanded to cover SNP variants that result in rare monogenic diseases with uneven geographic patterning (like PKU) to controversial behavioral phenotypes (homosexuality) to putative recent natural selection of cognitive abilities (Tay-Sachs).

The second half of the aughts saw a growing list of candidate genes predisposing to schizophrenia, and Doi et al argue in this article that these candidates should be investigated as possible heterozygote advantage variants. However, behavioral phenotypes are difficult to model precisely because it's easy to imagine that the context of a behavior would dramatically change its advantageousness. For example, Jones et al found that while homozygotes for a COMT variant were more likely to behave aggressively than controls, while heterozygotes behaved less aggressively. Arguably a good polymorphism for modern humans; a good idea during the paleolithic? Other candidates show poorer fertility in siblings and other relatives of schizophrenia patients (which flies in the face of a possible heterozygote advantage). Heterozygotes for a variant in KCNH2, a primate-specific isoform of a potassium channel found in brain and heart identified by gene screen, were shown to have lower IQs and reaction speeds than controls. The picture is far from complete precisely because of the number of gene candidates identified during screening over the past five years, on the order of a dozen.

An increasing number of psychiatrists and neuroscientists believe that schizophrenia is not one disease, that in fact it is a spectrum of related disease processes (like cancer) that stem from mutations in any of these candidates. Viewed in this light, the clinical picture of this devastating and prevalent disease (1% of the population) becomes clearer. For any anti-psychotic, only 50-60% of the population of schizophrenics will respond. (Imagine if a new ibuprofen-analog came out, and 40% of people who took it got absolutely no pain relief. Not only would you consider the drug a poor one, you would want to find out what's different about that 40% that keeps them from getting relief.) Regardless of the involvement of any of the candidate genes, schizophrenia is doubtless a multi-component disease process, so we should expect that there are multiple targets.

It has been argued by Harpending, Cochran, Hawks and others that not only has there been recent selection changing the frequency of genes between populations in historical or near-historical times, but that some of these variants identified are for genes affecting the central nervous system. For this reason it is all the more interesting that a variant of a schizophrenia gene candidate identified as strongly heritable in Europeans (FXYD6, an ion channel regulator) is not associated with schizophrenia in Han Chinese (Zhang et al).

A logical next step would be to start genotyping schizophrenia patients for the candidate genes, then record efficacy and specific symptom alleviation for different drug therapies. Professor Brian Roth at Duke has done exactly this for the pharmaceutical half of it, though to my meager knowledge, no one has as yet sat down to try to correlate the effectiveness of drugs in treating the positive and negative symptoms of schizophrenia provided by people who have different candidate mutations. It seems that we may be trying to treat different diseases with the same drug, and then wondering why it's only 60% effective. This is what I'm considering doing for my independent research project (a mini PhD required of medical students); if we can improve outcomes for schizophrenics with the therapies already out there, that's a big win for schizophrenia patients and their families, and conceivably a step forward in understanding how the architecture of the human brain results in consciousness.

Future Direction

2010-04-06T17:56:00.000-07:00

I've often found myself holding back from posting something for fear that a subject matter expert would come along and demolish it as either poorly thought-out or naive and ignorant of pre-existing work. But my to-read list isn't getting any shorter, and this isn't a journal article or a thesis. My reasons for writing this blog boil down to thinking out loud in public so I'm forced into some semblance of coherence.

Consequently going forward there will be more volume, with many posts possibly touching on ground that has already been covered by hard-working full-time philosophers and scientists. I hope to offer at the very least a unique synthesis from the perspective of a medical student interested in questions of consciousness, the structure of the universe and the impact of language on our knowledge of it, evolution in the abstract, and recent cognitive changes in humans in general. If you come back to the blog in the future and know of previous work, feel free to comment and direct me and other readers to primary sources.

Why Does Music Seem Faster During Semi-Conscious States?

2010-03-17T09:11:00.000-07:00

This morning someone in a nearby home decided to treat everyone to Joan Jett's I Love Rock and Roll at 8:30 in the morning. Laying there half-asleep and annoyed at the disturbance, I noticed how fast the song seemed. This is consistent with my memories of listening to music during breakfast in high school. Songs that seemed pretty peppy during breakfast seemed almost plodding if I listened to them in the afternoon. Why would this be? And how could we objectively measure the subjective experience of tempo to investigate this effect? For this purpose, introspection is a hard sell.

A Step Forward In the Binding Problem: Attribute Pairs

2010-03-09T20:22:00.000-08:00

A set of simple binocular-conflict experiments gives results strongly suggesting that we chain together sets of attribute pairs in order to bind together aspects of visible input into a coherent experience.

A Finite Universe Must Contain Finite Information

2010-03-06T14:32:00.000-08:00

I've recently been criticized for not using quantum computing arithmetic in my meaningless arithmetic post. I assumed that the amount of "stuff" in the universe amounted to rougly 10^80, using fundamental particles. Berkenstein and Schiffer* put a limit on quantum information in the universe at 10^122. Fine. In fact, let's say that even the various quantum computing cheerleaders are all hopelessly narrow-minded and we aren't even near the real upper limit. There is still an upper limit. The point is this: the amount of possible information about a finite universe (and therefore encodable by the universe) is also finite. It must be, if reality exists at all.

*Jacob Bekenstein and Marcelo Schiffer, "Quantum Limitations on the Storage and Transmission of Information", International Journal of Modern Physics v1, pp. 355-422, 1990.

Is Musical Dissonance Universal?

2010-02-28T15:39:00.000-08:00

I've often wondered about whether there is such a thing as a universally-recognized dissonant or harmonious musical interval. For example, Westerners seem to regard diminished fifth intervals as dissonant and tension-building (famous example: the Mars movement of Holst's The Planets). And indeed, six half-steps up a heptatonic scale, the ratio is the most destructively interferent, with a frequency that's an irrational ratio of the square root of two relative to the tonal. So what? It's not clear (to me at least) why that should sound "special" universally to all humans. Do Bushmen find it equally "tense"?

This interval has a history in the West. In the Middle Ages, Europeans weren't allowed to play this interval (the dreaded tritone) for fear that it would summon the devil, and regardless of the whether this interval represents a universal, surely today we're somewhat influenced by this antecdent. Okay - where did they get it from? A colleague of mine once threw out the idea that maybe a diminished fifth sounds like an animal in pain. Okay - so why does an animal in pain make diminished fifth-sounds? Do we have examples of scared or injured animals making such sounds? Universals based on physics that we understand today as semantically-gifted primates are usually not nearly as universal as we think they are, even within our species. The conservative position is to assume until proven otherwise that our associations with culturally institutions are just that - associations, programmed by experience.

This is why the following is so interesting.

(For the musically-challenged, compare to the Mars movement.)

Taking the starting and ending tones as the tonal, the high "note" that the wolf holds is a diminished fifth (compare to Mars Assuming the description is accurate and this is a wolf separated from its pack and trying to locate them, it's worth noting that a wolf under some stress tries to get other wolves' attention by using a diminished fifth interval. Note that wolves and other canines have a studied repertoire known "words", certainly not as plastic as the way humans use language, but nonetheless specific vocalizations that are repeated in the same contexts (separated from pack, just caught small game, get out of our territory, etc.)

Rationally Optimizing Pigeons

2010-02-26T21:49:00.001-08:00

Several years ago it was shown that dogs are less prone to the sunk cost fallacy than humans (couldn't find a non-gated version; pop science article here.)

The humiliation continues: pigeons are better than humans at the Monty Hall Dilemma. The question is whether humans lack whatever circuit is allowing pigeons to inductively (one assumes) approximate the logic of the Dilemma, or whether there's something in human cognition interfering with otherwise at-least-equal optimizing ability in this task.

A reasonable way of thinking about the first option is that for this specific behavior, for whatever reason, pigeons are more optimized, though for most things they aren't very good generalists.

Next step: finding out whether hamsters one-box or two-box on Newcomb's problem.

Altaic Pride!

2010-02-13T00:10:00.001-08:00

I ran across this online forum for discussing issues of pan-Altaic identity, complete with a silhouette of a ravaging Mongolic horseman. Apparently they're fans of the Ural-Altaic hypothesis because there's a Magyar forum but I don't see any Suomi; don't know what they have against Finns. Lapps are apparently right out.

I think in response all us Indo-European/Aryan/Kurgans from Reykjavik to Dacca should start our own club. Hear the call, my sisters and brothers in Moscow, Rome, Athens and Oslo, Tehran and Delhi and Tirana! (And not forgetting our brave Tocharian comrades who perished in the sands of the Xinjiang.) We'll organize it into chapters of a hundred each (satem or centum depending how you swing) and instill values of horsemanship, wheel-making and triumvirate-god-worshipping. We can only speak proto-IE at meetings, or failing that, Lithuanian, and I'm sure We can find another Lithuanian besides Marija Gimbutas to lead us. Activities include driving Basques into the Pyrenees, Dravidians out of the Indus Valley, and neolithics from other continents out of existence. I think we're onto something here!

Mathematical Coping Strategies for Schizophrenia

2010-02-04T19:28:00.000-08:00

Back in September I went to a pre-exam review held in a room other than our normal classroom. At one point when the instructor filled up one markerboard with chemical pathways, and rolled back the next one only to discover this:

This third one is blurrier than the other two but I've included it for scale.

In unison the class said "What?..." but the instructor was unfazed. "That's our local homeless guy," he explained. "He often comes into these rooms and covers the board with figures." I made sure to get these shots before they were erased, wondering if we had another John Nash.

Of course it's more likely that the man is just sick and these numbers are gibberish. (For the record, there's no way to tell just from finding numbers whether the person is schizophrenic.) I actually emailed the pictures to a cosmologist friend* to see if they meant anything (they reminded me of quantum numbers) but my friend said there was no order to them that he could see. Still, it's tempting to look for patterns on the principle that, if there is indeed any method to this madness, we could get to the concepts inductively. Once at a party, as a game I decided to play what appeared to be a single-player solitaire-like game. I moved the cards around randomly but with great apparent concentration (I don't even know the rules for real solitaire) and soon enough, someone started watching. "I think I have the rules figured out," he offered after a few minutes. (Given the limited input, he may well have.)

Beyond problems of induction, there remains the question of why someone with mental health issues would develop a habit like this in the first place. My best guess is that, since he's homeless on a university campus where social status accords with intelligence (or at least proxy indicators of it), by writing opaque patterns of numbers he can maintain the delusion that he's a misunderstood genius, at least as long as he's writing his number-patterns in empty rooms where they aren't critiqued by people with real math abilities. (A similar strategy would be to write a cognitive philosophy blog with few readers.)

A more interesting possibility is that by finding a way to occupy his attention with a task requiring high concentration and that uses non-diseased parts of his brain, this person has found a way to quell the other constant disturbances to his thinking and can gain himself a moment of peace. Of course this is speculation, but if it hasn't already been asked, this might point the way to novel therapeutic approaches.

*Speaking of status, please note the casual way I refer to my cosmologist friend, which means that I'm cool.

Existence and Consciousness

2009-12-21T12:45:00.000-08:00

To ask why there is something rather than nothing seems to assume on some level that it's less natural for the universe to exist than to not exist. It also assumes that some kind of existential inertia means that there will continue to be something rather than nothing.

This second assumption at least is not universal to humans, and is covered by Robert Nozick in the most effective treatment of this question yet. The Inuit believe that if hunting ceases, even for an instant, the universe will end. Several religious traditions hold that if at any given moment, at least one person somewhere is not copying their holy text, reality will sink back into chaos. These examples are interesting but are probably better explained as cultural technologies to keep people motivated in performing important activities, than as insightful cosmogonies.

Another question is whether it is clearly meaningful to ask counterfactuals about the fact of existence itself - whether existence had to exist - versus finite entities within existence. It is clearer that the pine tree outside my window, or you, might not have existed. In this way existence as a whole, the capacity for things to exist, is qualitatively different than a pine tree.

Changing gears to the ever-popular deep mystery, is it meaningful to talk about a universe that has no consciousness? Is self-awareness, a part of the universe experientially looping back on itself, necessary for existence? There is an intuition (which I share) that questions about necessity of existence and of subjective experience are getting at the same things.

James Cameron and the Problem of Reference

2009-12-20T12:44:00.000-08:00

Artificial languages are interesting, though I always find myself longing for some index of strangeness relative to the creator's language (pick a Native American language at random; is the conlang ever going to be more different than the creator's native language than the natural language is? I doubt it.) That said, James Cameron did it right for the Na'vi language in Avatar, reportedly claiming to have out-Klingon'ed Klingon. The linguist Cameron chose to create Na'vi summarizes its structure and during the preamble of the article, his interviewer states this gem:

"...since there is already tremendous interest in the [Na'vi] language, and some less-than-accurate information about it is currently floating around online, I asked Paul [the creator] if he could write up a formal description of Na’vi as a Language Log guest post."

The problem of reference is really a set of problems in different situations. The answer to this one is I think implicit and relatively obvious. Maybe we don't know if the current king of France is bald, but we do know whether Romeo is gay or Na'vi is agglutinating.

Flatland and Free Will

2009-10-22T19:27:00.000-07:00

In my previous post I asked why, if we do not have free will and the path of the universe is set in stone, we should have a seemingly privileged timepoint called "now". With no free will, there are no more degrees of freedom as you're reading this "now" "in the present" then there are degrees of freedom for something that happened ten minutes ago, or in 1588. In this setting "now" seems especially arbitrary and one wonders why nervous systems of this sort, i.e. that are constrained to one gradually changing temporal perspective, would ever appear - since events are all settled anyway. If we live in four-dimensional block of frozen space-time, why can't we see the whole thing? Why do we seem limited to one slowly shifting level within it?

Another way of looking at it (and responding to TGP's statement that "now" is a given) is to imagine a visit to Flatland. In Abbott's original conception, Flatland appears to three-dimensional beings as a plane in which 2-dimensional creatures like squares and circles are going about their lives, unaware (and unable to be aware) that above or below them, they were being observed by extra-dimensional beings. Abbott used Flatland as a way of arguing by analogy how fourth-dimensional objects would interact with and appear in our own three-dimensional universe (see the link for the full treatment).

If you look at our universe as four-dimensional space-time, then you can consider Flatland to not be two-dimensional, but three-dimensional plane-time. In a no-free-will Flatland, their universe would look to us like a tall box, with time-tracks - set-in-stone of every square and circle twisting through it like tunnels in an ant colony. If you wanted to be a three-dimensional sadist, you could climb up on a ladder and look at Mr. Square at the moment of his death in a two-dimensional hospital. Then you climb back down and again insert yourself into Flatland to find him enjoying lunch in a park the day after his twenty-third birthday. "You will die on the following date and time; I know, because I already saw it." Do you see why this is strange? From your three-dimensional standpoint, no-free-will Flatland is a giant, static sculpture. Why would the awareness of any entity in that block be constrained to any one plane within it?

By the same argument, in no-free-will space-land (where we live, if you don't believe in free-will anyway), we're stuck in a block of four-dimensional space-time. Fourth dimensional sadists are free to go scrambling up and down this block like you just did on Mr. Square's universe, except the fourth-dimensional sadists are looking for nasty tidbits to relay to unfortunate three-dimensional suckers like you. A fourth-dimensional sadist could pop in ninety seconds from now and tell you that you getting smooshed by a rabid slime mold on 19 July, 2025, and it knows because it already saw it happen. And in a very real sense, in a non-free-will universe, it already has happened. The disconnect is that you haven't experienced it yet, and in a no-free-will universe, that's what seems strange. If the events happening now are just as certain as the events happening then, why isn't seeing the future the same as turning your head to look at the other side of the room you're in? It's all already there.

An implication is that if we again assume a literal interpretation of multidimensional models of the universe, if the universe has a finite set of dimensions, it would necessarily be deterministic. The highest dimension would be a static one, and Mr. Square can't have free will if we don't.

Two Questions I Was Apparently Predestined to Ask

2009-10-21T22:09:00.000-07:00

To those who think free will is an illusion: why does it seem like we have free will? More to the point, why do we perceive a special point in time we call "now"?

Panpsychist Accounts of Consciousness Are Still Testable

2009-10-21T02:18:00.000-07:00

One challenge to David Chalmers' account of panpsychist consciousness is that it is untestable. If you argue that consciousness is everywhere (so goes the objection) then no observation can disprove your theory; therefore, it is not a sound theory.

Is this a valid objection? Chalmers is arguing that consciousness is a primitive feature of existence like charge or mass, that dimensional analysis by the four received basic units (charge, mass, distance and time) cannot in any combination "get us to" experience. One manifestation of mass is gravity. It is continuous throughout the universe; it is everywhere. Can gravity not be tested? The laws surrounding gravitation certainly can be, even though there is nowhere that gravity is truly zero.

If consciousness is (at least partly) epiphenomenal and supervenes lawfully on observable patterns in the material world, then these lawful relationships can and should be tested. The powerlessness of consciousness in epiphenomenal accounts (i.e. that our consciousness is caused, but does not cause anything, and we are in effect just along for the ride) is a problem that we've been wrestling with since Descartes and before, but it is a separate one. To argue the universality of consciousness does not make it any more untestable than gravity.

Hot Pics!

2009-10-08T07:05:00.001-07:00

Let me just be the first to say: that's one good-looking brain. In
particular, what a big hippocampus it has (all the better to remember you with):

In fairness, perhaps I am - it is - a biased observer of myitself. Perhaps the
study of the mind requires new pronouns.

I didn't just trip and fall into an MRI, I participated as a subject
in a memory task imaging fMRI study at my alma mater-to-be UCSD, by
the same group that wrote the voodoo correlations paper.

The worst thing about the experience? Tring to stay awake for the whole hour without being able to control any stimuli. I hope I gave them good data.

Resistance to Mutation and Preservation of Self

2009-10-05T09:54:00.000-07:00

One of the main principles in living things is the preservation of self at the expense of non-self, the maintenance of order by the absorption of energy, often at the expense of others. Of course, cells and most multicellular organisms are intentionless automata. But to intentional beings like us, whose self is identified with our consciousness and which is in turn dependent on the continued coherence of one physical form, it's easy for us to make muddy assumptions about the significance and stability of self in other organisms. It's strange that somehow our intention arises from the behavior of an assembly of these intentionless automata. We are at once watching, and the products of, a process that ensures that entities which take actions to make more of themselves are the entities we see in the world, and it's very difficult for us not to ascribe intention and agency to all living things, even prokaryotes, exhibiting clear functionality as they do.

You might not like it if your children end up being biologically different than yourself, but bacteria don't and can't care. If a cell doesn't care that it (or its offspring) may change radically if they mutate, then why do cells expend such effort preserving consistency of self? We should expect to see most prominently the effects of entities that copy themselves - but because entropy is always positive, it's only a matter of time before they change. It doesn't matter that "self" is not consistent over time, just that the cause-and-effect tree continues growing new branches. Yet all cells develop and retain elaborate mechanisms to prevent changes to their DNA. If preservation of a consistent self is not a real end, then why do they bother avoiding mutation?

Of course, the obvious answer is that as life becomes more complex, any mutation is far more likely than not to be injurious rather than beneficial. The more complex the organism (the more elements in a system) the more likely this probably is. Simple one-celled organisms could tolerate a slightly higher mutation rate, because they have fewer metabolic entities interacting inside the cell and few if any controlled external interactions with other cells. By analogy, imagine changing software across the entire General Electric family of companies, versus at a one-office specialty manufacturer. Therefore, in bacteria we should expect and do observe a higher mutation rate over time, and more diverse and innovative biochemistry at any one point in time. For example, some bacteria that can use sulfur as the terminal electron acceptor, converting it to hydrogen sulfide, parallel to aerobic organisms like us who breathe O2 as the terminal electron acceptor and convert it to water; in fact, there are families of bacteria where some use sulfur and some use oxygen (like Syntrophobacterales; imagine if some species of primates were found to be sulfur reducing, and the rest were aerobic - but as said before, you just can't expect that kind of flexibility at G.E.) Viruses also have been able to innovate in terms of nucleic acid reproduction far beyond what cell-based systems use, and they are notoriously sloppy in reproduction, far more even than bacteria (hence the necessary concept of quasispecies). Although the numbers probably wouldn't surprise us, it would be an interesting comparison to define some quantitative index of biochemical innovation-per-clade.

If cells do not expend effort commensurate with the likely damage from mutations, they will die, and we won't see their descendants. "Commensurate" means that the more likely a mutation is to be deleterious, the more an (evolutionary steady-state with respect to mutation) cell will spend to make sure it won't happen. Probable fitness cost is determined not just by the chance that it will be good or bad, but how good or bad it will be. At a guess, a deleterious mutation is probably likely, on average, to damage the organism's fitness more than the rare beneficial mutation will improve it. It should be possible to add up the energy that (for example) DNA Pol I and other proofreading systems in bacteria require for activity. If we assume that mutation costs are steady-state (a safe first approximation after 3.7 billion years of these molecules running around loose) then this number will be a good reflection of the fitness cost of mutations to these organisms. It's also likely to be higher for multicellular organisms and lower for viruses, on a per-base pair basis. Even if cells were capable of ensuring 100% fidelity, it's very likely that there's some point of diminishing marginal returns beyond which it's no longer profitable for the cell to bother with proofreading.

Now imagine a planet with particularly forgiving biochemistry, where mutations are equally likely to be positive or negative, and (further simplifying) the mutations are always equally good or bad. In this scenario (and any scenario more benign than this one), cells which expend any effort trying to stop mutations are wasting their time and are at a fitness disadvantage. Mutation would occur rapidly and there would be no stable lineages. Although you would eventually see reproductive isolation, you most emphatically would not see any one stable species or haplotype more than another, aside from some effect that those organisms closer to the mean (the ancestral starting point that sets the center of the normal distribution) would probably predominate in the early period before a stable population is reached in the bounds of their environment. At this time the allele distribution would shift to become truly random.[1]

In contrast, in our world, there are species whose gene pools are stable over long periods of time, relative to the behavior of the cells that make up those species. Therefore, altruism can appear if a gene comes along that gives its cell the ability to recognize other carriers and treats them preferentially, making it more likely to see that gene in the future. But in our imaginary world of neutral-or-better and therefore constant mutation, there are no stable species. Unless a gene arises that can somehow measure phylogenetic distance in general and act proportionally to it, there would be little altruism.

Mutation cost is not context independent, and the following consideration of how to predict and manage mutation cost might seem teleological, but it turns out to have real world correlates. Imagine (back in our own world now) that there's an organism that's doing badly. Some indicators of its doing badly would be that this it doesn't encounter many conspecifics (because they're all dead, or the organism has migrated into a novel environment) or that the organism is always starving, or it's under temperature stress. If you were that organism, and you had to make a bet about how optimized your genes were for your environment, you'd bet not very, or at least you'd bet slightly worse odds than if you were making the bet when you were doing okay. (There are some huge leaps there, but you're necessarily making a decision with incomplete information). Consequently the chance of a mutation having a beneficial effect in an environment where you're doing badly is slightly higher than in one where you're doing well, because you can be a little more confident that you (and your genes) are less likely to be near a summit on a fitness landscape. To put it in the extreme, loser organisms might be better off with just about any change. If there's any way for the organism to recognize its bad fortune, and then adjust how much it spends on proofreading - or in some way allow mistakes to be expressed - that's the time.

As it turns out, such a mechanism exists. Hsp90, a chaperone protein that has homologs in most cells, conceals mutations by correctly folding mutant proteins - except under restrictive conditions, like temperature stress. The mutation rate does not change, but in response to underperformance, Hsp90 can suddenly unmask the accumulated genotypic variation, which will suddenly appear as phenotypic variation. Rutherford and Lindquist neatly termed this phenomenon evolutionary capacitance[2], and later groups explored the concept in the abstact[3].

It bears speculating what other meta-selection tricks cells might have developed. Are there mechanisms to slow evolution in successful species? In other words, do consistently well-fed organisms and/or ones that are crowded by the success of their own species (for example, cultured bacteria or New Yorkers) spend more effort on tricks to slow evolution, in recognition that they may well be near a fitness peak, making mutations slightly more likely to be harmful? Cells in active, dense culture (but with sufficient resources) could be tested for mutation rate, controlling for metabolic changes occurring in response to crowding. The interesting result would be that they actually are mutating more slowly than before the culture became dense. [Added later: when I wrote this I wasn't aware of the phenomenon of quorum-sensing. Best known in bacteria, it also occurs in some metazoans. In fact some work has shown a link between quorum-sensing and mutation but it is not what I had predicted. That is, I had predicted quorum-sensing bacteria that mutated slower when they're in crowded conditions with conspecifics, because it's worth the energy to avoid mutation since they're more likely to be in an optimal environment. However, what has been observed in P. aeruginosa is that "high frequency" strains emerge which have had certain virulence factors induced in a way suggestive of quorum-induction, but that the quorum-sensing genes have been deactivated by mutation more often than would otherwise be expected.]

There are cases where organisms intentionally mutate, the best example of which is the adaptive immune system of vertebrates. (Note in the context of the prior argument that the mutation rate has not been shown to change with stress.) Lymphocytes produce molecules with specific randomly variable peptide sequences (one of these molecule classes is antibodies). Because this hypermutation always occurs in a strictly delineated stretch of amino acid residues within a peptide, the innovation is in effect safely inside a box. That such a clever and complex mechanism should first emerge in response to the constant assault of pathogens is probably not surprising. But if it appeared once - are there organisms with other kinds of built-in selection laboratories for other purposes? It's always easier to disrupt something than improve it, and what lymphocyte hypermutation is doing is disrupting pathogens. If there are any other such selection systems in biology, chances are that their function is to invent new ways to break other organisms, as with the adaptive immune system. A prime place to start looking would be venoms.

REFERENCES AND FOOTNOTES

[1] The thought experiment of the forgiving-DNA planet (with mutations equally likely to help or hurt) concluded that there would be no stable lineages. However, an added complication would be that mutations would result neither in reproductive isolation, or in speciation (though still not with stable lineages within each reproductive silo). Language, which often branches from a common ancestor and can be followed "genetically", follows a very similar pattern, since to a first approximation, phonological and morphosyntactical innovations are neutral to the function of the language. However, reproductive isolation does still occur (i.e., an English speaker can't understand a Dutchman or German) but there are also dialect spectra (i.e. Dutch and German have intermediates that are mutually intelligible to both). It's difficult to say objectively whether these spectra are broader or occur more frequently in language systems than in gene systems.

[2] Rutherford SL and Lindquist S. Hsp90 as a capacitor for morphological evolution. Nature. 1998 Nov 26;396(6709):336-42.

[3] Bergman A and Siegal ML. Evolutionary capacitance as a general feature of complex gene networks. Nature. 2003 Jul 31;424(6948):549-52. Nature. 2003 Jul 31;424(6948):501-4.

Malingering and the Deep Mystery of Consciousness

2009-09-27T21:46:00.000-07:00

This past Friday I was fortunate to see UCSD neurologist Mark Kritchevsky. It's hard to imagine someone more enthusiastic about medicine or research than this guy. As I decide what to specialize in, it's experiences like these that will add up to nudge me in one direction or the other.

The reason I'm posting is something that the dean of medical education at UCSD (Jess Mandel) said to Dr. Kritchevsky during the discussion that cuts straight to the heart of a) the deep problem of consciousness and b) straight to the way physicians treat and diagnose their patients. In the context of patients who present with acute anterograde amnesia (they can't form new memories, then the condition resolves itself) Dean Mandel recounted working with a neurologist whose favorite diagnosis was malingering. Every time someone came in with a strange set of symptoms, this particular neurologist thought they were faking. Dean Mandel's (unstated at the time) question was: if this is your go-to diagnosis, then why the heck would you go into neurology?

This also highlights something I recently heard from the neurologist V.S. Ramachandran (who I was fortunate to see earlier in the week as well), which is that if you see a patient and you dismiss their complaint as crazy - it's more likely that you as the physician are just not smart enough to figure out what's going on.

We're Living In the RNA World: Ribosomes Are the Meaning of Life

2009-09-19T22:38:00.001-07:00

[Added later: Clearly the Nobel committee was influenced by this post.]

Our view of the world beyond our senses is necessarily influenced by the instruments we use to investigate it. There is far more protein in cells than nucleic acid; and to the naive observer, the primary sequence of an oligopeptide (with 20 possible monomer units) seems a far richer source of information than nucleic acids, with only 4. Consequently it wasn't until 1928 with Griffith's bacterial transformation experiments that people began to seriously think about nucleic acid instead of protein as the heredity chemical. The final coup came in 1953 when Watson and Crick solved the crystal structure and provided a mechanism for DNA to be the biological information carrier.

It hasn't been until the last two decades that we've begun to understand the importance and diversity of RNA in Earth's biochemistry, possibly because RNA is harder to work with than DNA. Tom Cech and Sidney Altman received the Nobel for their work in the 1980s showing that RNA has catalytic properties stemming from its extra (relative to DNA) 2' hydroxyl. Besides its crucial role in the ribosome, RNA can also catalyze its own splicing.

This last observation was critical for anyone trying to puzzle out the chemical origins of life on Earth. DNA by itself in solution is actually quite boring; it just sits there. If life began with DNA, it would have stopped there too. Crick and Orgel speculated about life's chemical origins in the 1960s, forced to the idea that there must have been either an all-protein world (from which the transition to DNA-as-heredity chemical is unclear) or an all-RNA world. They also (pessimistically) speculated that, so unlikely were these events, that perhaps replicator chemistry could diffuse more easily through space than we realize so that it only had to happen once in any given galaxy for it to spread to other stars (panspermia, first discussed by Arrhenius over half a century before; for a longer discussion on one angle on panspermia, go here). Once the work on RNA's catalytic (and autocatalytic) abilities began, the RNA-world began to seem much more feasible. As we now know, pointing to its initial favorability, RNA splicing and even the attachment of amino acids to tRNAs both proceed just fine on their own. Free nucleotides are still the universal energy currency of cells. Urey-Miller's experiments showed prebiotic processes that could produce amino acids; these studies were soon supplemented by observations that nucleobases occur spontaneously on asteroids and can have plausibly originated prebiotically.

So far this has been merely a review of the RNA world hypothesis. It's anything but proven, but it's the best story we have so far, and we even have pathogens active today that are merely self-reproducing (though host-dependent) RNAs (viroids). The idea is that once nucleic acid had been established as the dominant replicator, some interaction occurred between RNA and DNA that moved DNA upstream in the causal hierarchy; that is to say, put it chemically in charge, possibly owing to its greater stability and conservatism since it's less reactive and exists as backed-up double-stranded template and is less reactive. Like the seawater-like salt concentrations found in the cells of Earth organisms, the activity of catalytic RNAs is a biochemical fossil, along with the messenger intermediates delivering sequence information to the ribosomes, energy carriers like ATP, and cofactors like NAD.

Segregation of Fitness Factors Within Membranes

Whatever the molecular basis for Earth's first chemical replicators, if they had a diffusible element to their reproduction, they had a commonly recognized problem to solve: how to sequester advantage. That is, if there was a developing RNA world where autocatalytic RNAs had developed a set of consistent interactions to polymerize amino acids and take advantage of a more diverse chemistry, how did they keep neighboring strands from benefiting? Imagine an RNA molecule has the trick of polymerizing a nifty oligopeptide that fetches ribonucleotides just incrementally faster than any other neighboring RNA in solution, making RNA-1 increase its numbers faster than its competitors - right? Wrong. That nifty oligopeptide is going to diffuse away and is just as likely to help any other RNA in RNA-1's neighborhood. So, from RNA-1's fitness standpoint, why bother? Until there's a closed feedback loop - until that oligopeptide is for some reason more likely to associate with RNA-1 more than RNA-1's neighbors - there's no point. (Frequently overlooked in this scenario is defense - RNA-1 also wants to keep its neighbors from eating up all the free nucleotides around it, or poisoning RNA-1's phosphodiester formation process, or even hydrolyzing RNA-1 itself).

The solution, of course, was the lipid membranes that now surround all cells (but not all replicators). Membranes form a self-nonself boundary and sequester diffusible benefits while providing a defense against chemical predation. The details of how this might have begun are still up for grabs, since there would have to have been mechanisms to open the membrane from inside and to gather and react to information from outside. While admittedly all this is highly speculative just-so discussion, the central point is that it's very difficult to imagine how a well-elaborated RNA-protein interaction machinery could have developed prior to membrane encapsulation of RNAs and their associated products.

What Was the Mechanism for the Transition to the DNA World?

If we assume that cells are "about" making more nucleic acid, then DNA's stability and conservatism does in fact seem to make it a better reservoir of information. Still, RNA world speculations tend to be a little short on details on exactly how such a transition could have come about. At this point, we're talking about a reproducing RNA molecule surrounded by a membrane with some set of RNA > protein chemical rules - in modern-day terms, we have a lipid bilayer with ribosomal RNA that can reproduce. The rRNA reproduces either on its own or with the help of an RNA-RNA polymerase, like the one influenza still uses today (in fact, many eukaryotes also have endogenous RNA > RNA polymerases).

There are at least two ways we can imagine the transition occurring.

A. An intracellular transition. RNA-protein cells developed a reverse transcriptase that gradually assembled a DNA-mirror of the RNA genome of the cells. If the advantage of such a DNA-mirror was as a back-up in the event that the RNA genome is damaged, this could only have been selected for with some mechanism to convert DNA into RNA (in modern terms, transcription). Because of DNA's conservatism, cells which relied more and more on DNA would be favored, eventually leading to a cell where the only reproduction was of DNA, not RNA. One test for this model is to look for a most recent common ancestor of RNA-dependent RNA-polymerases that is older than the last common ancestor of reverse transcriptases, which is in turn older than classical DNA-dependent RNA polymerases (with reference to RNA Pol I which transcribes rRNA), which is in turn older than DNA polymerases. It should be pointed out that most eucaryotic cells code for reverse transcriptases, some of which are critical for DNA maintenance, but most of which do not obviously benefit anything but their own reproduction (selfish elements), and which comprise substantial portions of eukaryotic genomes. Selfish elements and junk DNA are thought to be absent from prokaryotic genomes due to selection pressure on fecundity.

B. Nucleus-as-endosymbiont. To look at cells in a non-nucleocentric way, eukaryotes have 3 membrane-bound organelles containing genomes: chloroplasts, mitochondria, and nuclei. Nuclei are unique among these three in that they export nucleic acids to interact extensively outside their own membranes. If there is latitude even in a world of highly "committed" biochemical structures (like the modern one) for the survival either RNA or DNA viruses, we can presume that there would have been room for a membrane-bound DNA viruses in the membrane-bound RNA-world. A DNA virus could infect an RNA-only cell (similar to Philip Bell's concept of "DNA virus as ancestor of all eukaryotic nuclei"). DNA viruses in the RNA world would need reverse transcriptase for their reproduction; if we also presume, in multiple infections, a viral pickup of the RNA-cells ribosomal and tRNA RNA genes, they would eventually be incorporated into the nucleus - or today, the DNA molecule. The obvious objection here is that this assumes the first DNA cell was a eukaryote. First, the model could still function without a membrane-bound DNA molecule; we just couldn't explain the membrane-segregated nucleus in terms of endosymbiosis. Second, assuming phylogenetic relationships do not conflict with this account, it can be further argued that as with selfish elements and junk DNA, ancestral cells having greater complexity than modern bacteria is not implausible; prokaryotes are a more stripped-down later version relying on greater simplicity, driven by the need for fecundity. That is to say, since the advent of DNA cells, prokaryotes have lost their internal membranes, rather than eukaryotes having gained them. Third, and most important for later points, phylogenetic relationships for the eukaryotic LUCA based on ribosomal RNA are at this stage still unclear.

Both theories fly in the face of the central dogma, but the RNA world is the best supported account of the origin of life, and details of the transition to the DNA world are sketchy. In the first, DNA is merely a backup for the (at that time) true RNA genome - a set of rRNA and possibly tRNA genes - and the DNA backup gradually usurps RNA's role. In the second, a DNA virus remains permanently in a cell and absorbs RNA genes for what would later become our rRNA genes (but coded in DNA).

Speculation about pre-DNA world biochemistry can be disorienting. Taken out of their central-dogmatic context, the definitions of genotype and phenotype become less clear - in the RNA world they overlap strongly - and there seems to be no clear causal starting point in the information cascade. Which leads to the question: is there even such a clear starting point in the modern DNA world?

Why the Centrality of DNA? Cyclic Cause and Effect

Humans are limited in our pattern recognition abilities and when we encounter a new complex phenomenon we necessarily think of it in isolable cause-and-effect narratives. Consequently, it's useful in biomedical research to think of DNA as being at the top of a causal cascade that results ultimately in the reproduction of more DNA (or in the production of protein, which results in the reproduction of more DNA). In this view, cells and whole organisms - phenotypes - are survival machines that DNA uses to make more of itself. Put concretely, the function of an apple tree isn't to make apples; it isn't even to make more apple trees. It's to make more apple tree DNA.

Of course, no DNA molecule ever reproduced itself without the help of a host of specialized proteins, and every DNA molecule in existence today is causally downstream of a set of protein-and-RNA mediated events going back billions of years (just as all of them are causally downstream from DNA). This seems trivial, but leads immediately to the question: why is DNA alone given a privileged place in that cyclic sequence of events?

There are two reasons this is so. In the first half of the twentieth century there were a number of cyclic biochemical processes elucidated, among them the urea cycle, glycolysis, and the central dogma of molecular biology. In all of these, some entity or set of entities A gives B gives C, a clear and isolable stepwise set of inputs and outputs. Second, special in the case of DNA, there is information. The carbohydrate monomers in a glycogen molecule are chemically equivalent, a chain of zero-zero-zero-zero. DNA contains a quaternary code that has no clear function apart from its information content - it has a meaning, in terms of corresponding to amino acids. Cells don't consume it for energy; cells don't build walls or tubes out of it. It's there to be read, and the only thing that determines its meaning is other DNA molecules.

Two Thought Experiments, and the Meaning of Life

Is that last statement true at all? Of course not. Without even getting into epigenetic phenomena, the on-its-own-quite-inert DNA molecule doesn't do anything that proteins (and the RNAs that made those proteins) don't let it. Without those RNAs and proteins, DNA "means" nothing. The multiple inputs upstream from DNA, and the relatively pristine outflows downstream from it, make it a convenient point in the process for us to manipulate cells. DNA only matters because of what it means, and its association with proteins that actually do the work of the cell. That fact that its conservatism allows us to trace ancestry doesn't force us to conclude that it's the point of the cell. Thought experiment: if tomorrow, physicists found some bizarre particle physics technique to trace cells based on something in the lipid membranes of lysosomes, would that mean the cell was about lysosomes?

No, you answer - unless that particle physics tag on lysosomes correlated with some property of lysosomes that interacted with the rest of the world in a consistent way, like the DNA-protein feedback loop. Then you'd have something.

Forgive the mental biology, but thought experiments allow us to think about problems without the anesthesia of the familiar masking patterns. So indulge me: imagine that the world's first biochemical string theorist is working on an exotic n-dimensional model of physics and discovers that, unique among known molecules, DNA has a prominent, nonrandom structure in the higher dimensions model. Applying this theory to phylogeny trees, it becomes clear that in those higher dimensions, some new property of DNA, its n-dimensional conformation, and not its linear sequence, are actually more conserved over time, and correlates better with protein function, than its 5' to 3' nucleotide sequence. Wouldn't that be exciting? It would become obvious that we shouldn't be so hung up on the primary sequence; we would then reasonably conclude that this higher-dimensional structure is somehow what cells are "about" and what evolution has been selecting for.

Given the title of the post, you've probably guessed where this is leading. My argument is that life on Earth is best understood in terms of an RNA World that to us seems masked by the DNA it uses as a backup. At least as much as it's about DNA, life on Earth is about ribosomes. Apple trees are one way that ribosomes can make more ribosomes, as are slime molds, great white sharks, and koalas. We can think of the function of DNA as either a) a backup of ribosomes and b) one stage in the manufacture of all the rest of the ancillary machines that ensure survival of ribosomes. How is this different from making the same argument about any other cellular element, that the point of life is proteasomes? Not only are rRNA sequences (not to mention tRNA anticodons) the most conserved nucleic acids in living things, what is conserved is the structure of the molecule, over and above its sequence. Even more specifically than ribosomes, what is being preserved and selected for and served in a giant feedback loop by the rest of the structures in the cell is this consistent set of RNA-protein interactions.

There are many possible objections to this shift in viewpoints, and among them I will address two: first, the existence of viruses, which are non-ribosome-containing replicators. Viruses are "genes that got away" but have no independent metabolism (or ability to reproduce) independently of ribosomes. In terms of this ribosome-centric hierarchy, viruses are a peripheral curiosity in the same way as prions, which are proteins that reproduce their shape (and therefore physical properties) but also cannot reproduce chemically in the absence of ribosomes; of course, in terms of biomedical relevance to human life, viruses are anything but a curiosity (but this may serve to obscure their hierarchical triviality). On the other hand, Viroids are RNA-only replicators which can, in fact, reproduce without ribosomes, using only RNA Pol II, and some are autocatalytic.

A second objection made frequently is that the structure of rRNA and the protein-nucleic acid that structure mediates (and the rich chemistry that sprouted around it on the young Earth) were driven by thermodynamics - that there's only one way to build the interaction surface, and only one set of 20 amino acids that could ever have been chosen. If the shape and activity of a ribosome are really just thermodynamic fate, then there's no heredity information in rRNA - no heritability information, no meaningful travel over time in the fitness landscape, and no possibility of "frozen accidents" that commit a system to climb toward local optima, any more than there is for a star or fire. Yes, fire spreads and consumes fuel, but the commitments of dumb physics force them to behave the way they do; there's no difference in the flame on a birthday candle whether you lit it from a lighter or at the edge of a burning pine forest. One way to test the question of whether ribosomes are stuck in one shape would be to run synthetic biology experiments with simple ribosome systems where you swap out the 20 legacy amino acids to search for a more robust set of monomers, with some kind of feedback to allow selection. But that would be an extremely complicated experiment. I rather think that the burden of proof is on the claimant who argues that the anticodon system we ended up with is necessarily the universally best one, and that RNA-descended aliens from Alpha Centauri would necessarily use the same set that we do.

SUMMARY

- Our understanding of molecular biology and the evolution of the cell is constrained by the useful conventions we use to study chemical processes in the cell. Despite the wide acceptance of the RNA World hypothesis, we still view life on Earth as being about DNA.

- The transition from the RNA world to the DNA world was mediated by either development of reverse transcriptase and RNA polymerase activity, or an endosymbiosis event involving a DNA virus infection and uptake by the virus of rRNA genes.

- DNA is best thought of as a back-up of a) rRNA and b) all other types of catalytic molecules (today, mostly proteins) all of whose function is to ensure the survival of rRNA.

- rRNA genes are the most conserved among living things; notably, the structure of the rRNA itself is even more conserved than the primary sequence.

- A better way of thinking about life than considering it to be about DNA is to think of it as about the propagation of ribosomes, or specifically, about propagating a specific set of protein-RNA interactions mediated by a specific type of chemical structure.

Cool Evolution Find: Fossil Virus

2009-07-23T12:07:00.000-07:00

Not in stone of course, but in crocodilians' genomes. ERV covers well. Question for evolution, as she puts it: if this virus was good enough at what it did to work its way into a genome, why does it apparently have no descendants today? Two possibilities come to mind: 1) its descendants are still around, but we haven't discovered it yet (remember Nannarrup hoffmani? A whole new genus of metazoans found 7 years ago in Central Park, New York?). 2) the chance of becoming an ERV do not correlate over time with fitness.

Consciousness, Reduction, and Memory

2009-07-22T13:48:00.000-07:00

A tool that I think we underutilize in the hard question of consciousness is the idea that if some entities are conscious, and some are not, then there is a boundary between the two categories. My suspicion so far is that any close examination of this boundary inevitably becomes a reductio ad absurdum, and the boundary evaporates, regardless of the examiner's initial intentions; and once the boundary has evaporated, we're left with the unintuitive non-assertion that there is no reason to think everything doesn't have some rudimentary consciousness - or the non-starter that nothing is conscious. The first assertion led Chalmers to his famous and misinterpreted statement about conscious thermostats.

You don't think thermostats are conscious? Fine. What about dogs? That's a slippery slope; as a furry, warm blooded vertebrate primate, you're subject to some pretty powerful biases about what the signposts for self-awareness are. Roger Penrose once (half-jokingly) conceded insects to the world of unconscious Turing machines, and Dan Dennett immediately challenged him: why? In other words, if dogs are conscious, why not octopi, crabs, E. coli, and the Melissa virus? Where's the line, and what is it? A 40 Hz wave? Unsatisfying, to say the least.

The point is this: if you believe that consciousness only occurs in what we on Earth call living things, then you must also believe that at one point it did not exist. Fair enough: so where and when did the first glimmer happen? It's not obviously a meaningless question to ask whether the first consciousness appeared in a trilobite scuttling about in a seabed on the piece of continental plate that is now Turkmenistan, a minute before sunrise on 28 June, 539,640,122 BCE (I think it was a Tuesday). It's tempting to dismiss point-of-origin stories like this, but the alternative is either to accept some provincial point-of-origin since the Big Bang, or accept that consciousness is a spectrum, in which case we're back to the thermostat (or to none of us being conscious). Both alternatives are counterintuitive, but modern science is littered with such choices; not surprising given how far we are out of our depth, i.e. collecting food, finding mates, and running from predators in East Africa.

So far I have not explicitly stated the materialist assumption that consciousness is related only the the matter of the entity in question, and how that matter is arranged - but there is the stickier question of within what limits that matter can vary and remain conscious. By that I mean, my brain is physically different from yours, and from a monolingual Greenlandic woman's. You could rob each of these three entities of their current level of consciousness by making physical changes to them, but all three were different to start with, so how do you know they were all conscious? Another not obviously meaningless question is to ask whether a capacity for consciousness must necessarily permeate an entire species. Why assume the conscious/non-conscious boundary follows species boundaries? Maybe on that fateful June 28 in the early Cambrian, there was just one single conscious trilobite, surrounded by zombie trilobites. And maybe some humans are conscious and some aren't.

This may seem to point the way to a reductive program, to test the boundaries of what can be conscious. We can't go looking for the boundary with a time machine to see where it all began, and of course even if we could there remains the challenge with the hard question that we have to rely on first-person accounts we get through third person reports - we can't build a consciousness meter to wave at trilobites, and they can't tell us that the sunrise was pretty. And even if they did it doesn't prove they experienced joy at seeing it; the whole problem is the inviolable subjective first-personness of it. But since we are assuming that consciousness relies on matter and arrangement (i.e. nervous systems) in a reproducible way, in a pattern that at least some humans can understand, we can still reductively investigate alterations of the material state of the basis of consciousness using human first-person accounts, in ways that don't veer off into other problems of behavior as such investigations often do. This still won't answer the hard question but it will at least show us to what things the hard question can apply.

We can't quite cut out brain tissue and ask people whether they're conscious (the idea is to restore the previous state, when you know they were conscious as near as that can be known by a third-party). But what we can do, and have done is study cognitively abnormal humans who can communicate their experience. These break down into 1) people with some disorder, either through trauma or congenital condition and 2) people who change their brain chemistry either from some activity (meditation, extreme exertion) or consume mind-altering compounds. With #1, people usually remain in the same state. With #2, these occasions occur under very uncontrolled conditions and we have very limited options ethically - "go run a hundred miles then meditate for a month and tell me what it's like" - and scientifically - there are only so much agonists for receptor X and the brain doesn't cooperate in the way they're distributed.

If we have anything to say about it hopefully the numbers of people in category #1 will drop. If as time passes our ability to reversibly under- or over-stimulate parts of the brain increases, as I hope it will, then I hope future neuroscientists will be able to pick from a suite of compounds that block specific tissues in the brain (not just receptors) from interacting with the rest. Of course, this program might not be able to tell the difference between basic requirements of consciousness, and the provincial arrangements of our own brains - or primate, or mammalian, or vertebrate brains. (Note: I am not advocating kidnapping of and experimenting on aliens, though if you have one, call me). It seems to me the two components of consciousness in our normal cognition that would be of immediate interest and are relatively isolable in anatomical terms are memory (sensory, short- and long-term) and goal-orientated behavior, specifically with regard to pain and pleasure.

Regarding reductive investigations of memory: is it possible to remove consciousness in a way that is reportable later? In other words, say you find a molecule that shuts off only the here-and-now experience, but not anything else, including memory. While the subject is under the influence, she's same as she ever was, lucid, talking, responding - a classic philosophical zombie. You give the wash-out. She reports that she now remembers the conversation, remembers what happened while she was "under", but somehow didn't experience them at the time. Can this even be meaningful?

Science fiction thought experiments of memory implants come to mind: in the movie Blade Runner, androids that live only four years are given childhood memories so they don't realize they're androids; did they experience those childhoods? The reverse situation - that is, experience, but no memory, known as anterograde amnesia - is the subject of the movie Memento (category #1, abnormal human), and does occur in the real world, but there are also abundant real-world examples in category #2, as anyone who consumes alcohol can learn. A personal account illustrates this. At a friend's birthday party I overindulged. Among the many escapades that evening which charmed and delighted my fellow party-goers was the following groan I emitted while sitting in the hot tub: "Oh god, I'm going to be sick...what's the point of blacking out if you have to experience it anyway." At which point they wisely shooed me from the tub, and my prophecy was realized.

I tell this story not to concern you more for my liver than my brain, but because the interesting part is that I don't remember it. I did black out - I know this only from (effectively) third-hand accounts. Thanks to my ethanol-clogged NMDA receptors, I have no memory at all of that event (or many others that evening). Did I experience nausea? Where did the experience "go"? What evidence do I have that at that moment I was not a zombie, even to myself? One solution is that I'm silly to worry about where the experience goes - that at least in human brains, experience requires only sensory memory (in us, a second or so), or that it requires sensory and short-term memory (in us, five to ten minutes). But is there a drug even in principle like the one in the experiment above that could have saved me from the experience of nausea but preserved the memory? That's not an entirely dispassionate question, becuase I would make that trade in a second.

The second area of investigation - goal-seeking behavior - raises questions about whether it is meaningful to talk about consciousness in the absence of pain or pleasure. I'm not talking about full-body analgesia; I'm talking about not experiencing psychological discomfort in response to thoughts about seeing their kids at the end of the day or worrying about your mortgage. Granted, that's a little more involved than questions about memory.

I think a continuing focus on specific parts of the brain in a reductive search for absolute boundaries of consciousness - if indeed there are any - is wise for more than just theoretical reasons. Any research program that ignores its sources of financial support is one that won't move along very quickly. The hard problem of consciousness, while I consider it the central question of philosophy and science, is not one that promises any immediate application that can return effort invested in it. I'm obviously sympathetic to philosophy and science for its own sake, or I wouldn't be writing this out of personal passion. But we all want to see progress on this question, and being able to sell the research based on applications to Alzheimers, ADHD, and schizophrenia would go a long way to obtaining support and public awareness. Technology that we don't yet have that will require money to develop - or, technology that we do have that requires money to obtain and use. And in the end, I can't think of a better outcome anyway than that this research could end up helping human beings suffering with cognitive disorders.

Monkeys Can Respond to Grammar-Like Patterns in Sound

2009-07-20T12:24:00.000-07:00

Article here. Essentially, tamarin monkeys showed a capacity for recognizing a pattern of phonemes, and then recognizing when a novel pattern appeared (if an affix was used in the wrong place).

Primates can frequently recognize language-like stimuli when exposed to them, but whether they can be trained to generate them is another question. (And we know they don't generate them spontaneously.) It seems to me there are two take-homes here. First, that many primates (including those not even that closely-related to us) have the hardware for linguistic pattern recognition. This raises the question of whether other linguistic substrates delivered over a time sequence could evince similar responses: chains of images for example. It would be interesting to compare human and non-human primates in these experiments (with sound and non-sound grammar).

The second, and to me more interesting, point to investigate is to what degree non-human primates can associate the patterned-sounds they're hearing with semantic content. No, it wasn't a concern at all in this experiment, but it's crucial to the development of language. While Endress et all conducted this experiment with particular reference to grammar acquisition, a model of vocabulary acquisition in human children uses much the same pattern-recognition skill: children learn words by looking for sequence rules, and take notice when they're violated. A chid learning English for the first time has no way to know that "word boundary" is two words, and where the dividing line is, until they figure out that English words don't often start with "db"; in fact words don't even have that sound combination so much (and of course they hear the words separately). The tamarins were doing some form of this.

What the tamarins can't do that childre can - or at least no one's shown that tamarins can do it, and I don't think anyone expects it - is that once they've parsed out the elements and learned the order they usually occur in, they can build a network and assign each element to an object or attribute they see in the real world. I wouldn't be blown away if a tamarin learns to be "surprised" (as in this experiment) by an "o" coming at the beginning of a word, as opposed to at the end. What the tamarins won't ever learn is that the -o ending means that the word in question is an object that is receiving action, as opposed to performing it. Yet somehow every normal Japanese child learns exactly this by age 5, and lots of other such content-sound relations as well.

Animals clearly can associate a few sets of sounds with concrete, specific content. Anyone who has ever had to spell out "W-A-L-K" to a fellow human in front of a dog knows this. But the extent of language perception in non-human animals is an interesting question because it gives us a chance to do some comparative biology with reference to the following questions. How how many of these sets of sounds can the dog (or the tamarin) learn? How generalizable is the ability - i.e., given the internal states of the animal as they reflect the outside world, how broad or distinct are the categories that can be covered by a single signifier - your dog understands tree, but does it understand redwood? Plant? How complex a relationship between signifiers can the animal construct, e.g., can the animal tell a difference between walk, walked, and don't walk? And to what degree are these things related - that is, do human children get a mnemonic benefit from pinning the sounds they learn into a richer network of semantic content? Pinning down these differences to the activity of physical structures in our brains will go a long way to understanding how we acquire and process language.

Bias Bias

2009-07-20T12:14:00.000-07:00

So we're biased against seeing our biases: while it's nice to have experimental verification, this should not be surprising, else our biases would be subject to examination and we could get rid of them.

A frequent subtext of bias studies goes is this: "Look how distorted our perspective of the world is. It's good that we study these tendencies so that maybe we can diminish or eliminate them, and people would have a less distorted view of reality." It would be useful to ask what would humans be like without these biases. How would individuals behave differently? What would society look like? Aren't some of these biases fairly obvious beneficial self-deception strategies that evolved as a result of conspecific competition; would cutting them out of some humans (but not all) actually result in individuals handicapped in the survival and reproduction game, and wouldn't similar strategies redevelop over time? Most importantly, without our biases would we be happier? Is it meaningful to talk about waving a magic wand and re-wiring the brain to eliminate these biases, or are they so deep-wired as to require much more profound commensurate changes to retain a functioning central nervous system?

What Do Serial Killers and Suicidal Rats Have in Common?

2009-07-19T04:35:00.001-07:00

Serial murder is such an astonishingly maladaptive behavior that I've often speculated whether we're not seeing a) a gene that, when heterozygous, is adaptive, but when homozygous, can lead to this behavior, or b) a toxoplasma gondii-like infection.

Toxoplasma gondii is the pathogen that makes the rodents it infects behave (basically) suicidally around predators, like cats; the cat eats the rat, the organism survives in the cat's gut, and when the cat defecates, it spreads more Toxoplasma. (I first read about this organism and the incredibly specific behavior an infection engenders in the work of Daniel Dennett, who is a big fan of this organism as a metaphor for other replicators.) Now it turns out that humans infected with Toxoplasma are also more likely to behave dangerously, judging by car accident rates. (Hat tip to Marginal Revolution).

Humans engage in many apparently maladaptive behaviors (serial murder among them) and this story gives us no reason to conclude that serial murder is the result of an infection, but it does show that even in humans, complex behaviors can be affected by an organism in ways similar to the other host species we've studied. Behaviors like serial killing are so inexplicable that hypotheses about their origins should include infection as a possible etiology.

I grant the full-on speculative nature of this post, and even if serial killers are infected with a T. gondii-like pathogen, then it remains to be explained a) whether the infection-induced behavior would have been the same in our hunter-gatherer ancestors (how can you be a serial killer in a band of 25 people?) and b) how exactly the behavior would improve transmission, which is clear in the case of rats and cats.

Cows, Free Will, and Nuclei

2009-07-02T16:39:00.000-07:00

I'm often amazed at the stupidity of cows. I encounter these mooing morons frequently on trail runs that pass through pasture lands. Frequently there will be a cow standing astride a path that I'm running along at constant speed, gazing in dumb fascination at me as I approach: 200 meters, 100 meters, 50 meters. Even though I've now been approaching the cow at constant speed in a straight line in the open for the last two minutes, it's often not until I'm within 10 meters that the cow will suddenly realize I'll eventually reach its position, and that's when it suddenly turns in a panic and runs away.

Of course, in no technical sense was my continuing along the same path clearly "predestined", even if you don't believe in free will - any number of plausible forces could intervene to stop me - I could decide to stop because I just ran up a steep hill, or a meteor could hit me, or I could turn left and run into the grass for no reason - but the cows' failure to move until I'm almost on top of them certainly does not result from any nitpicking of causality. Possibly the cows are conditioned by the ranch hands they see more often, and which do stop before they get too close. Or, funnier and just as likely, they're just too damn dumb to recognize the pattern (my straight-line path) and extrapolate it to realize that I'm going to get to their position - not until I'm barely ten meters away.

For the sake of argument let's explicitly assume that there is something in the universe that is not predestined to happen in a certain way at a certain time - and if you'll accept any example, you'll accept that the decay of a single radioactive nucleus fits the bill as non-predetermined. Sure, trillions of them decaying together will fit a pretty nice predictable curve, but it's hopeless to try to predict the decay of individual nuclei; nuclei of the same isotope are, by any measure we know, absolutely indistinguishable, and they decay randomly (that is, without any pattern that we can recognize). The question, then, is: is an individual decay really non-predetermined? Or are we cows that just can't recognize the pattern that they're following? Most importantly, is it possible in principle for a non-pattern-recognizer to ever tell the difference between these two alternatives?

Because the universe contains a finite number of elements, infinite computing power isn't possible; therefore there will never be an infinitely powerful pattern recognizer. Consequently, the question asked in the previous paragraph becomes very important. If it is not possible for a non-pattern-recognizer to tell the difference between inability to recognize a pattern in a system, and actual non-predetermination in that system, then we can never tell if we have free will, or are merely stupid.

Is underperformance in the presence of superiors a deceit strategy?

2009-06-23T15:33:00.000-07:00

Humans often perform worse on tasks under pressure when in the presence of superiors. This is interesting because evolutionary psychology arguments can be made for the opposite effect (performing better in the presence of superiors). This effect is apparently not a voluntarily controllable one.

A study at John Moores University shows that other primates underperform on problem solving tasks in the presence of superiors - but interestingly, this experiment was designed to evince deception.

This study aimed to correlate monkey species' ability to deceive with the strictness of their social structures, and they did so (positively). One of the researchers argues that the less deceptive primates are more like humans, because their social groups are fluid - but that's only been true for a few millennia. Hunter-gatherers fifty thousand years ago would have found it much more difficult to decide to join a new foraging band because they didn't like the scene they were in. So, social group plasticity have been much lower for most of the history of our species, making the ability to deceive more important than these researchers might otherwise argue.

Furthermore, the smarter a species - that is, the better a problem-solver it is - the more important are its interactions with conspecifics, and the less important are its interactions directly with the environment. Who cares if you can forage for tubers - you're an entertainment lawyer! So not only the potential to, but the usefulness of, deception becomes greater in proportion to the intelligence of the animal.

This is not proof that underperformance in presence of superiors in humans is definitely an unconscious deceit strategy, but the existence of the behavior in other primates, along with its probable greater importance in humans, is reason for further investigation.

Your Day Is Over

2009-06-11T17:38:00.001-07:00

Get the divergence time for any two animals or groups of animals. Awesome. It's like Google Maps to the natural history of Earth. Hat tip to ERV.

Numbers That Have No Meaning

2009-06-01T00:20:00.000-07:00

The Planck-time - the smallest slice of elapsed time that we can currently conceive of as physically meaningful - is about 5 x 10^-44 seconds. A year is 31,557,600 seconds long, and the universe is about 1.4 x 10^10 years old. This means that since the Big Bang, there have been about 8.8 x 10^60 Planck-times so far - 8.8 x 10^60 instants, to put it crudely and with apologies to Einstein.

Now let's count things. Defining only fundamental particles as things, in the standard model some have thrown a dart and come up 10^100 particles, one googol. That'll work for now. The vast number of permutations with this set of individual things is 10^100!. A scary big number, but still finite. Of course, if you count photons as things, photons vastly outnumber quarks and leptons by a factor of at least a billion. Fine; let's make it 10^209!. Then the number of instants in which things can have happened (8.8 x 10^60) multiplied by the possible combination of things in each instant (10^209!) is the number of things that can have happened so far in the universe. Let's call this huge but still finite term Ω.

You may argue with the figures I've used or even the rather ham-handed back-of-the-envelope calculation here, but my point is that the number of things that can have happened so far is finite, and so is the number of things that can ever happen, whether you expect a Big Rip or a proton decay at some point 10^10^70 years from now. In fact the real number of things that can have happened up until this point must be much smaller than what I've proposed; every arrangement of those 10^209 elements is constrained by the previous arrangement as a result of things like the speed of light and the conservation of energy.

So now we have Ω - so what? What's interesting is that there must also be a number Ω + 1; a number which exceeds possible events x things to describe - a number that cannot refer to anything real. Yes, Ω will get larger as time goes on, but it will still be finite, and arithmetic will always allow Ω + 1. That's nothing new; examples abound of theoretical computations that could not be completed before the expected decay of protons, even with the resources of the entire universe's fundamental particles marshalled for the task. Many of them involve board games.

So this means that mathematics - even arithmetic - is richer than it needs to be to describe our impoverished universe, and that there exist numbers which are simultaneously logically valid but which can in principle never have meaning in physical reality. My intuition is that this has less to say about reality than it does about mathematics, which is a particularly effective form of language we are just in the early process of developing to understand the world.

Prehistoric Crossings that Could Have Happened

2009-05-13T18:15:00.001-07:00

Cryptohistory is full of accounts of putative pre-Columbian contacts between New and Old World Civilizations; their frequency in lay literature and on the web is dependent much more on how interesting the encounter would be than on how likely it is to have happened based on the evidence.

For example: Zunis are a linguistic isolate with a bizarrely high frequency of Type B blood. They must be the descendants of lost Japanese pilgrims! Or - it's possible for a late iron age Norwegian to sail west from South America across the Pacific, approximating Inca technology - therefore, the Pacific could have been settled by South Americans! We know better today, half a century later, from DNA and linguistic evidence. But did Polynesians come to South America? The discovery of conquistadors' texts that said there were already chickens there suggested this, but so far DNA analysis has been inconclusive. For my money, the only decent evidence so far for trans-Pacific contact prior to Europeans is the linguistic and technology evidence in raft-building by the Chumash on California's central and southern coasts.

But all of these contact theories are relatively recent, in terms of prehistory. The major gene distributions and language families that we see today are the echoes of earlier migrations, the most famous of which is the crossing of the Bering Sea land bridge by Siberians to populate the Americas, 20,000 years ago or more. But we know that sometimes paleolithic people crossed water too: the first Australians were able to cross channels that were still tens of miles wide during the last ice age at least 40,000 and perhaps as long as 70,000 years ago. In Japan, at least by 30,000 years ago, people were able to make two > 50 km open water jumps across the Tsushima Strait. Consequently there's one other place where I'm curious as to why there isn't more discussion of why a water crossing didn't seem to have happened - the Strait of Gibraltar.

What is now the Sahara was much wetter as the Earth's climate shifted away from its most recent glacial maximum, and only now are we starting to understand the diversity of the people that lived there. One site in particular (the Tenerian culture at Gobero in Niger), only discovered in 2000, has burials dating to 7500 BCE. These were pastoralists, and it's clear that a greener Sahara could have supported a much denser population of pastoralists then than now. We invariably assume that Europe was colonized from its southeast, through the Middle East. Why could "green Saharans" not have made it across the Strait of Gibraltar to Iberia?

We know for certain that neolithic Afro-Asiatic speakers (the Guanches) settled the Canaries. Of course the interesting possibility is a connection to the Basques. It's possible that some Tenerians did colonize Iberia, but that water crossing is an effective enough barrier to gene flow that the genes coming through the Middle East into Europe swamped the Tenerian genes. A quick test would be an analysis of Basque mitochondrial DNA against Guanche and Gobero samples; if it has been done at this point I'm not aware of it.

Sculpture before Image

2009-05-13T15:20:00.000-07:00

In September 2008, archaeologists from the University of Tuebingen in Germany discovered an inch-long ivory carving of a nubile woman that by carbon-dating is on the order of thirty-five thousand years old (to be published in this week's Nature). After reveling in the impact of looking at something carved by cognitively active humans living that long ago, my next thought was whether sculpture pre-dates flat visual art.

The oldest sculptures we have are thousands of years older than than oldest visual art. The oldest cave drawings we have are from Chauvet, which are at most 30,000 years old. This is an outlier. We have over a hundred Venus-type sculpture artifacts older than that, dating from the period 25,000-29,000 B.C. (see Venus of Dolni Vestonice). This still isn't a huge sample, and maybe images don't age as well as sculpture - but more importantly, it's reasonable to expect that even older images and sculptures are both waiting to be found not just around the Alps and Pyrenees but throughout Central Africa.

Alternatively, maybe sculpture really did come first. This makes sense. To us today, drawing is easier than sculpture because, while we're are familiar with both, creating a drawing recognizably representing an animal is less time-, material-, and skill-intensive than creating a sculpture. Now that we have lightweight drawing mediums (nowadays including electrons!) drawings are also more portable. But to someone who has never seen either medium, a sculpture may seem less difficult to "get your head around". A woman is a three-dimensional thing; so is a piece of ivory. The leap to representing a woman (or horse) as a flat, untouchable image on a surface - as if they're trapped under ice - must have seemed a real abstraction.

Phonetic writing systems today offer another example of a mode of representation that is anything but obvious to those never before exposed to it. Ask any literate native Chinese speaker. Representing utterances phonetically rather than semantically - that is, using sound-based rather than meaning-based symbols - is so abstract, when though about from first principles, that it's amazing anyone thought of it at all. It's therefore not surprising that there was a gap of millennia between the idea of regular correspondence between visual symbols for words and phonetically defined ones, although the non-obviousness of alphabets is difficult for modern literate Westerners or Middle Easterners to fully appreciate today.

The benefit of phonetic systems, once you invent them, is that they are much easier to learn - hence why in Japanese book stores I go to the children's section and read about cats and bears in the 42 basic phonetic characters of Hiragana, but I'm hopeless if I try to read the grown-up prose in yesterday's Asahi Shimbun. Learning those 42 basic characters in Hiragana are on the same order of difficulty as the 26 in the English Roman alphabet and 33 in Cyrillic, but wholly different from the number (and visual complexity) of the 3,000+ you need to for the newspaper. It is also not surprising that as adults, it's more likely for monoliterate ideogram-readers to learn an alphabet than it is for monoliterate alphabet-readers to learn an ideogram system. While there may be some influence behind this asymmetry from the current realities of history and economics, I doubt it will change very much. Similarly, now that we have drawing in addition to sculpture, we demonstrate a preference for it - because it's easier and cheaper.

So did sculpture pre-date image? Carbon-dating of the available evidence supports this so far, and it's consistent with the development of human representation systems for which we have more direct evidence. I expect that there are more caves around the Pyrenees for us to discover with paleolithic artifacts. Chauvet Cave was only found in 1994. I predict that some of these caves will yield more carved figures that are older than any known drawings.

Free Will and Chocolate

2009-04-19T00:08:00.001-07:00

Kant talked about heteronomy, the condition of an individual's being at least partly under the control of influences other than his or her own reason, and therefore not truly exercising free will. Of course this early Enlightenment ideal strikes us as a bit naive today, and obviously we recognize that we are animals with a physical form.

But there's no need to put such extreme, stark requirements on free will for its exercise to be unclear. A perfect example is my own appetite for chocolate. At the moment, I have avoided all forms of chocolate for 16 days. As far as I can remember in my life, this is a record. In the past when I wasn't so lucky I would declare "no chocolate for one month", and then three days later at 7-11 I would break down and get a Hershey bar.

Now, clearly in those 3-day cases I was unable to follow my prior edict, but at that moment, chocolate is what I wanted. And I acted on the urge. How is this not free will? Because the urge came from a pre-conscious animal drive for sugar and fat, and/or conditioning from previous purchases at that same 7-11? If ultimately what we call reason, and our entire executive center, is a slave of the passions as Hume suggested and as seems to be the case, how could it matter whether I was acting directly on an animal urge or on some long-term plan that was dictated by animal urges?

Language as Behavior

2009-04-14T13:13:00.001-07:00

There's an old Indian fable that goes like this:

A wealthy, wise traveler who spoke a dozen languages came to the kingdom. He used his learning and wit to quickly attach himself to the Raj as an advisor. The problem is that so fluent and perfect were all the tongues that the advisor spoke that no one could tell his country of origin, and this concerned the Raj's guards. "What if he is a spy from an enemy kingdom?" The guard arranged meals between the advisor and visitors from a dozen different lands, speaking a dozen languages; during all of them, the advisor conversed with them as if he were a native, and none of the visitors could detect even the hint of an accent. The guards became desperate, sure that their Raj was allowing his court to be infiltrated by enemies. Finally, one guard had an idea. At lunch one day, one of the guards took the teapot from the servant and said "I'll handle this." Instead of pouring the tea the guard dropped the full pot of hot tea in the advisor's lap, who promptly leaped to his feet, cursing in Persian.

What does it mean when you stub your toe and grunt or curse? Even if you form a coherent monosyllable, in strict semantic terms it doesn't mean anything (unless you somehow misapprehended your injury as being causally related to copulation, feces, or a deity). It's "meaningful" in the sense that it means, behaviorally, you are suddenly and surprisingly in pain, but that's not linguistic. These kinds of nonsemantic utterances are problematic for philosophers of language because they have no truth value, yet they're clearly important to our linguistic lives. In fact they form a kind of instinctive, basic core of our ability to produce language.

When we think about language, I think we don't take nearly enough advantage of the other slightly less bright critters in our phylum. A few days ago I was at a shoreline park and noticed something interesting. There was a group of plovers pecking the wet sand at the water's edge, when two comparatively massive geese came lumbering toward them. The plover on the side of the group closest to the goose piped a little squeaking call, and all the plovers turned and flew away. Later on, I saw a single goose approach some plovers, and again one plover made the same call; again they flew away. Had I witnessed the ploverese word for "goose" or "fly away"?

Of course not. I observed the ploverese equivalent of what you say when you stub your toe: it's behavior. There's no real free will or cognition involved in either act, any more than there's free will when you move your arms to help you run. The plover call is a totally non-arbitrary act that can only be said to represent anything (have any meaning) insofar as birds call to each other as a warning - but that's the same kind of meaning that your toe-stubbing curse has.

Clearly humans were not always the paragon of animals, and there clearly must have been a time when our ancestors were limited only to non-semantic set-in-stone behavioral vocalizations, and that's why we often look at chimps. In one instance, researchers reported that when a new food (grapes) were introduced, the chimps began to make a different "excited" sound at feeding time. Could this be the chimp word for "grape", at least in that lab? Or are the chimps just excited in a different way, anticipating a different taste, of grapes? Is there a difference?

This is my central thesis, that language developed as, and remains at base, an expression of states of the the central nervous system. It is mostly a description of what's going on inside, not what's going on outside. Of course, in any organism that wants to get its DNA into the next generation, there will be some connection between the outside world, and the organism's internal state (which produces observable behaviors, including language) - but that connection can never be perfect.

This statement attacks the unstated assumption that the primitive content of language is semantic content. That is, that in its most basic form, language began as "grape", not as some excited (but nonsemantic) hooting about getting a certain kind of food. Perhaps the better way to look at language is as a set of behaviors reflecting internal states - vocalizations indicating the fear or hunger or aggression of the organism, which were themselves responses to the outside world. As nervous systems become more complex, the internal states of those nervous systems were more and more able to discriminate finer slices of objects and events in the external world, and therefore the vocalizations became more complex. Eventually, the ability to retain, process and pass around information would be selected for, and at that point there would be an evolutionary feedback loop. In plovers, the language behavior is extremely non-arbitrary and low-resolution by virtue of being filtered through the bird's simpler, less-networked nervous system. Consequently, there can be no subtle gradations in that call of the goose's size or speed or location or disposition, because the plover has no internal state to reflect all those dimensions (even if it can be aware of its own location or disposition).

This immediately puts several problems on new footing. First and foremost, the relatively late spread of genes that influence language (40,000 years ago) makes more sense when you realize that a complex nervous system with the ability to react more "finely" to the outside world would have to appear first. Certain kinds of basic verbalizations (like exclamations of surprise) become less of a puzzle when their lack of semantic content is excused. It is also less surprising that commands are in most languages the most basic form of verbs. Refocusing on language as a reflection of internal states takes some pressure off the Hegelian conundrum of definitions: when I say "I want pizza", there's no question about what "pizza" is to me, although that variable may correspond to a state in you that's different. In this light it's amazing that words align with things in the real world as well as they do - but it's good enough for government work. It may be objected that this places the truth value of statements entirely inside the subjective world of the speaker, but in principle, you could look at the neuron pathways active during an utterance to see whether that really is what they meant by "pizza" when they said it.

Cognitive Closure

2009-04-13T18:21:00.001-07:00

Usefully defined, cognitive closure is a phenomenon where concepts or thoughts which are otherwise logically valid or accurately reflect some pattern in the real world are fundamentally unthinkable. It is assumed that limits to cognition in humans are owed to some commitment in our neuronal architecture and that other conscious beings could conceivably think thoughts which are for us imaccessible. Colin McGinn is well-known for discussing the concept in the context of arguing that the consciousness is one such cognitively closed arena.

There are at least four senses in which cognitive closure is trivially true; first, in terms of signifier transparency, or trivial closure due to habit. That is, I am a native English speaker, not a Japanese speaker, so when I look at a woody-stemmed plant ten meters tall with leaves and roots I cannot have the experience of thinking "ki" without it being polluted by thinking "tree". In fact in a real sense, I question the idea of a "literal" translation. There is just no way to convey in English the exact tone difference between German Sie and du or Spanish Usted and tú. But this is nitpicking; no one has exactly the same reaction to every object in the world either, based on their personal experiences (like Dennett's argument that the red you experience can't possibly be the same as the red I do). Sapir-Whorf notwithstanding, this is not a kind of closure that interests us.

Second and equally trivial are closures due to linear hardware limitations (storage or bandwidth limits). You and I can't multiply 151,692 by 65,778 in our heads. I don't think this is what we're talking about either.

Third, and slightly more subtle, is trivial closure due to lack of pattern recognition ability. Imagine I break the Mona Lisa's face into one of those Wall Street Journal dot portraits of a million black-and-white pixels, a thousand by a thousand, and I give it to you as a row of a million black-and-white squares, locking you in a room until you can tell me what it is. The chance that you would figure it out before your death is low, but as soon as I tell you "It's the Mona Lisa's face in rows of pixels" it would be mere minutes before you had arranged it properly. If that's cognitive closure, then your dog is similarly closed to language. He's been listening to you talk for years now and all he's figured out is treat, walk, and bad. In fact when Chomsky discusses this term this is the sense he means.

It's worth pointing out that even these so-called trivial examples, while not as eerie as the almost Lovecraftian way we think of closure, does in fact bring with it practical consequences. There is no reason to think our intelligence is at the upper bound of what is possible (I certainly hope not); a superintelligent alien conceivably could hold digits in memory and manipulate language in a way that puts us in the role of the aforementioned golden retriever. It is often objected that we now have machines to do our cognition for us, which is a mistake of definition: regardless of whether cognition is computation, it is also an experience. (Another trivial form of cognitive closure is that everyone's cognition is off-limits to everyone else's, because our nervous tissue is not contiguous: not the concept of the the first vs. third person divide, but the experience of it).

When you punch a bunch of big numbers into a calculator, you're really handling a cognitive black box; yes, you can check the output for consistency, but the cognitive experience of multiplication is closed to you, even though you can check the output for consistency. Dennett has argued against hardware-limitation closure based on the increased use of prosthetic apparatus (computers) allowing us to perform the calculations, but unless the calculator is wired to your brain and you experience the calculations, you're not experiencing them.

There are many trivial ways to understand closure but they are frequently confused with the deeper idea that there exist inferences or connections that accurate describe parts of the world which somehow our architecture obscure from us, not out of hardware limits, pattern recognition, mere linguistic habit, or isolation of tissue. The concept (which I call "strong cognitive closure") suggests far more fundamental limits to our minds, and because of the limited and klugey nature of our brains I'm very tempted to think such a thing may occur, but without a formal way to evaluate closed concepts, if cognitive closure of this kind does exist, the first question is whether we could even have an experience of it. That is to say, would we come to a point in a train of thought, be aware that said thoughts are coherent, but be frustrated and unable to proceed? Or would we be utterly ignorant that there was any barrier that we had just bounced off?

McGinn is arguing the first case in his discussions of consciousness, because we're all aware of our frustration with the topic of consciousness and its seemingly incommensurable first vs. third person modes. The problem here is in how we distinguish between something that is truly cognitively closed and something that is just a very thorny problem that we haven't solved yet. In other words, is there a way we can ever know for sure that something is cognitively closed?

For example: if we solve the Grand Unified Theory, we'll know it's not cognitively closed to us. But until we do, maybe it is, maybe it isn't. For that matter, even after it's solved and a handful of physicists understand it, it will remain cognitively closed to me and most likely you as well - unless there's a way to show there's a difference between not understanding something right now, and not ever being able to understand it in principle. Another chance to clarify what "real" cognitive closure is: certainly my brain as it is now constructed could not understand the G.U.T., because I lack the math. If the G.U.T. is cognitively closed to humans, the structure of our central nervous system assures that no amount of training could sufficiently alter the brain to accommodate the ideas. Again, is there a way to differentiate between these two?

It's worth pointing out that we're increasingly appreciating that the human mind works more like a maze of funhouse mirrors than a crisply calculating abacus - it is full to bursting with blindspots, hangups, and heuristics that may not have been much challenged a hundred thousand years ago in Africa, but today frequently get us in trouble (ask the psychologists - anchoring, sunk cost fallacies, you name it).
The encouraging thing, both in terms of self-actualization as well as in investigating cognitive closure, is that we have "meta-heuristics" which allow us to occasionally be aware of of our own shortcomings in such a way as to avoid those pitfalls. Our minds are clearly inelegant Rube Goldberg contraptions, but that doesn't mean were are helplessly clueless that this is so.

It seems to me that if there were understandable criteria for strong cognitive closure - if we had a list of consistent principles and could say "Anything that requires mental processes X, Y, and Z to understand can not be understood" - well, then we could understand it. Therefore if such a thing as cognitive closure does exist, it would necessarily include itself as one of the incomprehensibles, and consequently, the second case would obtain - that is to say, that we cannot be aware of cognitive closure when it occurs. If so, then the discussion ends here: we can never know if we've encountered a closure, and it would be exactly as if cognitive closure did not exist.

A theologian once said that God was so perfect, He didn't have to bother existing. So it is with strong cognitive closure. Having trouble understanding your credit card statement, or written Chinese? Weak (trivial) cognitive closure. Unfortunately I can't point you to an example of strong cognitive closure, because whichever position you take on it, for practical purposes, there isn't any.

Cognitive Enhancers

2009-04-13T01:47:00.000-07:00

In Nature, Greely et al write in support of cognitive enhancers. Justin Barnard responds negatively.

We certainly owe ourselves a frank discussion of the potential individual and societal impacts of the increasing use of cognitive enhancing psychoactives; unfortunately Barnard is not contributing to this. As is often the case for such arguments, Barnard appeals (unclearly) to the idea that cognitive enhancement is "unnatural"; that humans, and human nature, are not to be evaluated solely in terms of information processing ability. But Greely et al do not make such an argument. Their aim is to explore a powerful (and even disruptive) medical technology in terms of expanding its potential benefits, and mitigating its risks. It would be equally incoherent for Barnard to object to improved agricultural technology by saying that there is more to man than satiating hunger. Of course there is. This concern is quite wide of the mark, which is that if we might make our world better with a new technology, we owe it to ourselves to explore that technology.

One problem with arguments like Barnard's about the ethics of self-alteration is that there is always a spectrum. Is it immoral for me to get that third cup of coffee if I'm flagging a little at 3pm? Caffeine is not only a well-established cognitive enhancer, its effect on physical tasks like long-distance running are well-known as well (here's my recent personal experience in a marathon). Was this "unnatural" of me? Or is it unnatural to raise your kids in a house with lots of books, because access to knowledge and reading adults has been shown to boost the kid's achievement later?

Let's look at another field of endeavor where these judgments are made constantly. Competitive cyclists and marathoners train at high altitudes to boost their red blood cell counts. In what way is relocating to a marginal low ppO2 environment for the sole purpose of training "natural"? Athletes who do well in these sports typically have naturally high red blood cell counts to begin with, and high EPO levels (the hormone that triggers blood cell production). So they inherited a few stretches of DNA with less stingy regulatory regions that I did. Is this fair? If it's unnatural for me to just take EPO, how about if I can boost my own endogenous production? This was a nifty trick developed a decade ago by TransKaryotic Therapeutics, a Boston biotech whose transposon technology got locked up by the legal team of EPO-hoard-ward Amgen. Still have the "ick" because it's a drug? Then let's review: going to a mountain so the thin air wrings more red blood cells out of your marrow is okay, but doing the same thing by coaxing your hormone production up (using your own genes!) is not okay. Aren't these distinctions starting to seem arbitrary?

Clearly, whatever the rules are regarding performance enhancement in a sport, they have to be consistent within that sport; and clearly, commonplace ninety-minute marathons will not have the same impact that chemically-induced geniuses will. This is exactly why the Nature paper recognizes that we have to proceed cautiously and safety is paramount - as with any other chemical we develop and ingest to improve our lives. For instance, the currently-available cognitive enhancer Adderall is merely a mixture of amphetamines. It's speed. It's entirely appropriate that access to this addictive psychoactive substance is controlled. It's also entirely appropriate that we explore the ways (if any) it's acceptable for this drug to be used by healthy people as an enhancer. Maybe for Adderall there are no such ways, but every molecule is different. That is to say, it's completely inappropriate to throw out a whole technology because a single tool has too sharp of an edge.

As a more speculative aside, it is my prediction that by the end of the twenty-first century, medicine will run out of diseases which can be treated by waiting until something breaks and then stopping the out-of-control process or aiding an atrophied one. There are many diseases which result from basic design flaws in the architecture of our tissues and the machinery of our cells - accidents waiting to happen - like back problems, hip and knee issues, cancer and autoimmune diseases. Fixes for these problems will require not only germ-line alterations, but even more profound re-engineering of the fundamental cogs and gears of metabolism. Whether we're ready for such an enterprise is a discussion that will likely happen after you and I have both returned to the elements. I make this point to say that I would not necessarily endorse such a move, and Greely et al are clearly not talking about anything so radical either, despite Barnard's anxiety. The Nature paper is advocating a search for better cups of coffee, and a sober discussion about their risk-benefit profile in general. That's all. Before we toss out an entire potential approach to bettering the human condition, the onus is on the advocates of Barnard's position to articulate their counterarguments more clearly, and with fewer appeals to vague romantic intuitions about the meaning of life.

If Descartes Were a Masochist

2009-03-20T15:38:00.000-07:00

True story. I staggered into a bar one Sunday at lunch to meet a friend. I was staggering not because I was already drunk, but because I was sore from a 22-mile run I'd done the day before through mountainous terrain.

"You look great," he observed as I stiffly winced my way up onto the bar stool. "Want to go to the museum later?"

"Can't. I'm going for another long run this afternoon."

"Why?" he asked, not unreasonably.

I responded much less jokingly than this statement should be delivered: "To punish my legs for hurting me."

He thought about this and drank some more beer.

Finally he offered, "You should study the mind-body problem."

"Why?

"Because you have it."

Naked Mole Rats Live a Long Time

2009-03-17T17:38:00.000-07:00

So it says here. One other interesting thing about these disgusting creatures is that they're the most eusocial of all mammals. So that leads to the next question: do entomologists have anything to say about the comparative lifespans of the highly eusocial hymenoptera order of insects?

Why Do We Worry About Consciousness?

2009-03-16T13:48:00.000-07:00

When humans find a new object or material or aspect of the world that behaves contrary to their expectations, it arrests our attention, and we poke at it to learn more. Primatologists use extended attention as a measure of "noticing something is strange" from chimps and babies - when something strange happens, they stare at it for longer. No doubt this explains the fascination with shiny nuggets in stream beds humans have exhibited for millennia, when we encountered the only metal to be commonly found in its unoxidized form in nature owing to its high redox potential.

It's this same pattern-recognition itch that motivates my, and I would guess most people's, investigation of consciousness. It's like diving into a lake and missing, every time. It is irredeemably strange that each of us encounters consciousness every waking moment and yet are at a loss to explain it coherently. It can be said that a rigorous understanding of consciousness would be the apex of the Enlightenment project, combining self-knowledge and how the universe works with a tool to alleviate suffering and the human condition.

It's useful to remind ourselves of what the big puzzles are from time to time. In investigating consciousness, I'm really most interested in the deep mystery of consciousness, also known as the sunset problem (why does the experience seem to be like something), or what Chalmers refers to as the hard problem. The mechanics of how pain, behavior, even free will (if it exists) arise are not that interesting compared to the deep question of how and why subjective experience exist at all. Saying that the brain produces consciousness (like Searle) does not eliminate the problem, and explaining it or its states away (like Dennett and the Churchlands) does not account for my own experience. I feel pain, and I desperately wish I could explain it away.

The most intractable aspects of the Hard Problem are outlined below.

1) Accessibility of experience. There is something it is like to be me, and I can never know whether there is something it like to be anything else. This is the first person vs third person barrier. It also seems to be something that can't be shared between conscious beings - we can never know if another is conscious. For all I know, everyone could be a zombie.

2) Consciousness seems to occur in some things but not others. Why? What are the prerequisites for subjective experience? Because of the zombie problem, can we ever answer this?

3) Consciousness seems conceivably separable from complex behavior. That is, there is no obvious reason why something would have to evolve actually having the experience of pain, instead of just being programmed to avoid pain. Is this a coincidence of life as it happened on Earth, a side effect so to speak? Or does consciousness play some necessary part?

4) Cognitive difficulties with discussion. Try to answer the question "What is consciousness?" We have an innate difficulty in discussing the topic, whether this comes from a lack of terminology or some twist of our nervous system that obscures the matter. Very bright and earnest individuals have trouble even understanding each other's basic definitions. We can't discount the possibility here that our problems in understanding consciousness result from our making assumptions that are so profound that we aren't yet aware of them.

5) There is no conservation principle in consciousness. This is a less discussed point, and may not even be that interesting. Still, it is a property of consciousness that makes it unlike other phenomena. In contemplating this point, I understand what is most likely the second most popular reason to believe in an afterlife: it seems counterintuitive that all this sensation I am experiencing could suddenly cease due to a simple collapse of chemical gradients, without violating some balance in the universe. Note that I am emphatically not arguing for any spiritual interpretation here - but this seeming paradox could be useful in learning more about consciousness, and it is undoubtedly part of what encourages humans to believe (incorrectly) in some life separate from the physical.

Consciousness and Dimensional Analysis

2009-02-02T02:13:00.000-08:00

Benevolent physics instructors often give their students exams with "gimme" questions. Often these gimme questions have responses that can be easily ruled out by dimensional analysis: you know it can't be choice (c), because the answer to the question has to be expressed as an intensity, so it will have to be in Watts per square meter, and (c) is in volts.

What's always amazed me, when I've thought about it, is that the whole material universe seems to be describable (at least so far) in terms of just four fundamental dimensions: distance, time, charge, and mass. Quantum physicists may point out other properties, but the point remains that a small number of simple physical dimensions describes our world.

What's also interesting is how some of these units can seem intuitive or counterintuitive to our mammal brains. That things accelerate in terms of distance per time squared I "get". That intensity breaks down to kilograms per seconds cubed makes no sense at all to me. The change over time of the acceleration of mass change? Really?

Of course, we use lots of units that are created out of convenience and that aren't explicitly represented in terms of their basic dimensions. However, this doesn't mean they can't be reduced in principle, just that it's just not normally useful to do so. Temperature is a good one. Although in SI it's considered a basic unit, in reality it's a measurement of molecular motion distributions (mass, time, and distance). Any quick and dirty material unit, even ones in economics, project management, you name it, can be reduced to these basic dimensions.

Things become far more interesting when we look at units measuring subjectively perceived quantities. Scoville units for pepper heat and visual analog scales for pain are two examples. Of course, your internal state can change, and change your subjective "reading" from time to time; I hate IPA beers, particularly Sierra Nevada, but the beer I had at the end of the Big Sur Marathon was one of the best I ever tasted. Taste is a reaction between a substance and your nervous system, and your nervous system can undergo changes - for example, the changes wrought by 26.2 miles of dehydration and depletion of carbohydrates.

But the problem I'm interested in is not the variability in the test almost always found with subjective measurements. Let's return to Scoville units. For the sake of argument let's say you're a brilliant gustatory neurobiologist, and you've devised an equation that, given all the physical data about capsaicin structure and concentration, states of the neurological system it's interacting with (number of nerves on tongue, how they connect to various parts of the brain, emotional state, etc.), you can consistently predict the Scoville assessments that your taster will report. How do you break down perceived heat into these dimensions?

You can't; correlation is not the same as equality. Yes, you can break down into those basic dimensions the chemical process of capsaicin molecules binding to receptors in your mouth. But even if you assume an absolute and inviolable 1:1 correlation between chemical state and sensation - that is to say, an exact correlation between material and experience - the experience still remains an incommunicable property. Consequently the idea of dimensional analysis might give us a new way to worry at the problem of the relation of consciousness to matter.

This last statement is by no means uncontested. The incommunicable components of experience are usually called qualia. Searle draws a hard and fast distinction between third-person measurement and first-person experience but somehow does not brand himself a property dualist. I myself am uncomfortable with the term but have to apply it to myself until I find a way out of it, and find Searle's insistence that he is not one perplexing. Hardcore physicalist/functionalists would say that the heat of a hot pepper is, in fact, an incommunicable property, and therefore not real (technically, this is what Daniel Dennett is telling us). This is problematic for anyone who has eaten a habanero, as I have, because I can tell you for sure that it hurt. It's also problematic for anyone who has not eaten a habanero. You can try to imagine what it might be like, but the fact is (to your profit) you have never felt it firsthand.

This problem has also been phrased as part of Frank Jackson's Mary's Room argument. Let's say you'd lived your whole life in a room that was entirely black and white (including through some devious trick of bioengineering, your own skin, hair, tissues, and fluids). While in that room you train to became a neuroscientist specializing in vision studies, and you learned everything there was to know about color perception, although you'd never actually experienced color. (There are major problems with these "everything there is to know" kinds of suppositions is the often require - I'll address this later in my own response to Searle's Chinese room - but let's go with it for now.) One day the door is opened, and you exit the room, to see blue sky, green trees, and red roses. Do you learn anything? Or (I would argue, a different way of asking the same question) do you experience anything new?

There certainly are cases of people deprived of certain kinds of input earlier in their lives suddenly being given that input. A good deal of our perceptual wiring is biologically driven and will set itself regardless of what stimuli we happen to receive, but a good deal of it is molded in response to experience. For example, there is one case of a man blind until his forties whose vision was restored by an operation. He reports that he cannot tell people apart by faces - which you would think would be hardwired in social animals like humans - and that, having learned to ski while blind, he finds the visual input while skiing to be confusing and keeps his eyes closed.

Consequently you wonder if, after spending your life in this room, you would be able to perceive color at all, or if your senses would have become attuned to shades of gray in such a way as to keep your internal world the same as people who lived in a color world. That is, what the rest of us would call light gray, you experience the same as what we would call lavender.

Where speculation fails us, concrete neurological reality often steps in. And in fact, there are people with us today who are always partly in the black-and-white room: they're colorblind. But we're not about to do eye transplants for philosophical experiments, so hold that thought. Most of us are familiar with the idea of synesthesia, which occurs when sense information crosses channels (e.g. sounds are tasted, colors are heard). Although most people only experience this when using hallucinogens, particularly HT2A agonists, synesthesia exists as a constant condition in some people, perhaps most famously in the writer Vladimir Nabokov. You might ask if people who have been blind since birth see colors when they use LSD, and the answer is yes. And you might also ask whether colorblind people who also happen to be synesthetic experience colors outside the domain of their unfortunately flawed visual apparatus. The answer is yes, and these colorblind synesthetes are fully aware that they have never seen these colors associated with objects in the real world.

Since a colorblind person's isolation from their blind-colors is even more complete than the black-and-white neuroscientist's, it's not a huge leap to expect that you would also experience something new on exiting the black and white room. You could make similar arguments for someone who had never been burned, either by fire, or by capsaicin in their mouths from a habanero.

So we're back to Scovilles as an experiential measure, not able to be reduced to material units. You are still a brilliant gustatory neurologist with your exact 1:1 correlation between capsaicin receptor occupation and neurological state (measurable by mass-charge-time-distance) and Scovilles. So many nanomoles of capsaicin, controlling for temperature, pressure, some measure of how many nerves are in your tongue and how much of your brain is attentive to it - yes, you can predict 100% of the time what the Scoville rating will be when a new subject comes to your lab to taste peppers. But the units are still not the same as your eating a habanero. Per the thought experiment, and the reality of colorblind synasthetes, you still learn something by experiencing the habanero.

Physical quantities can be communicated and replicated without losing anything - they are interchangeable with information. But experience is locked inside your own consciousness, and in fact you can never in principle know whether anyone else actually experiences the world, or are just "zombies" with all the outward appearances of experience. Imagine you stick me in an fMRI and make me eat a habanero. While I'm howling in pain inside the machine, for some masochistic reason you jump into a neat gadget you built which takes my brain activity as input and feeds it to you, so that you experience what I'm experiencing. And suddenly you're howling with my pain of a few hundred thousand Scovilles. Was I feeling that? Or am I just a zombie, and your machine is producing in you, the one conscious being in the world, the sensations that I would be feeling if I were truly conscious?

All this identifies qualia and the world of subjective experience as fundamentally different from and incommensurate with the material world, built as it is of units with convertible dimensions. I am forced to take a dualist position, even if I am assuming (as does David Chalmers) that experience is wholly epiphenomenal.

Panpsychist positions like that developed by Chalmers focus on consciousness as a primitive property of the universe supervening on (epiphenomenal to) matter, and it is to this position that I usually subscribe. Chalmers frequently points out problems with nonpanpsychist assumptions about consciousness that lead us to treat it differently from other phenomena in the universe, for example in its sharp discontinuity and its origination from zero, with no clear demarcations or even the suggestion of how to measure it. I will write more on this later.

One interesting question about reality that panpsychism may begin to answer is in the question about what gives natural laws their "fire" - that is, it is possible to imagine a universe with different fundamental constants. What pins those constants down? What makes the laws of nature what they are, and relate to each other as they do? For example, why aren't there three charges, or another fundamental dimension? It is possible to conceive of countless hypothetical universes, but why are the ones that govern our lives "real" instead of being what-ifs with no power over reality when these laws are just information? I once put these questions to a cosmologist and was offered a modern take on Spinoza's argument for the existence of a supreme being: there is something that has as its nature to exist, and its internal logic has to work out consistently in order to exist. But this still doesn't give us a satisfying answer of why the laws of the material universe - equivalent to mere information as they are - are real and have fire. The answer may be that there is some basic qualium, which I would argue is the pleasure-pain principle, a property of the universe itself, just as mass or charge are. Without pleasure or pain, the other qualia, which otherwise would emerge in structures that become more and more complex, cannot exist at all; this explains why experience would necessarily appear as a part of the life of living things, when there is no clear evolutionary or other story for it. Without pleasure or pain the information of the universe has nothing to mediate it into experience and make it "real".

[Added later: funny cartoon about dimensional analysis here.]

Maybe A Cold Earth in the Eoarchaean Isn't A Problem

2008-12-23T23:47:00.000-08:00

For two decades or more, biologists have had a problem with astronomical and geological accounts of the early sun's evolution. The problem is that our models show that the sun was probably too faint to maintain liquid water on the Earth's surface until sometime in the Paleoarchaean, and solid ice makes a poor chemical reactor for early evolution. In 2007 Daupha et al showed evidence of mineral deposition 3.8 Ga under conditions of high-pressure carbon dioxide, which of course means a probable greenhouse effect at that time on Earth.

Because we've always assumed early Earth was a hot Earth, the conventional wisdom of the evolution of life on Earth has held that the last universal common ancestor (LUCA) of all living things was a thermophile, much like the biochemically weird things living in deep sea vents or those prismatic mats at Yellowstone, which is why an early cold Earth doesn't seem to fit. But a snowball or at least near-snowball ancient Earth may not be a problem after all. A recent publication by Boussau et al shows that LUCA was a mesophile, best adapated to life at temperatures below 10 degrees C.

This is also consistent with the idea of an RNA world, since RNA is unstable at low and high pH, and even less stable at high temperatures than DNA. Interestingly, the LUCA of eubacteria and archaebacteria does look like a thermophile, consistent with temperature estimates of later periods in Earth's history when the ocean was thought to be on average 80 degrees C (about 3.5 Ga). The resolution of ancestors at different time depths is permitted by the use of two methods, one based on GC content of the genome and one based on amino acid substitution.

This is biological and geological convergence at its finest; Lyell and Darwin (and Woehler and Mendel) would be proud. We now have a consistent story for the evolution of the sun, the atmosphere of early Earth and its effect on surface temperature, the temperature adaptation of the earliest cells and the switch from RNA to DNA. The next step is to explore the period 3.8 to 3.5 Ga, to look for evidence of skyrocketing ocean temperatures; not inconceivable given a thick CO2 atmosphere and a sun that was still booting up. If our picture of Earth's surface temperature in that period is accurate, we can also start to ask whether rising temperatures were the selection pressure switching the early biosphere from RNA to DNA.