#6. Mental Illness as Communication [neuroscience, genetics]

NE   GE

Red, theory; black, fact

The effects of most deleterious mutations are compensated by negative feedback processes occurring during development in utero. However, if the population is undergoing intense Darwinian selection, many of these mutations become unmasked and therefore contribute variation for selection. (Jablonka and Lamb, 2005, The MIT Press, "Evolution in Four Dimensions")

Basic Darwinism Is So Inefficient

However, since most mutations are harmful, a purely random process for producing them, with no pre-screening, is wasteful. Raw selection alone is capable of scrubbing out a mistake that gets as far as being born, at great cost in suffering, only to have, potentially, the very same random mutation happen all over again the very next day, with nothing learnt. Repeat ad infinitum. This quarrels with the engineer in me, and I like to say that evolution is an engineer. 

Evolution of Evolution 

Nowadays, evolution itself is thought to evolve. A simple example of this is the evolution of DNA repair enzymes, which were game-changers, allowing much longer genes to be transmitted to the next generation reliably, resulting in the emergence of more complex lifeforms.

What I Would Like to See

A further improvement would be a screening, or vetting process for genetic variation. Once a bad mutation happens, you mark the offending stretch of DNA epigenetically in all the close relatives of the sufferer, to suppress further mutations there for a few thousand years, until the environment has had time to change significantly.

Obviously, you also want to oppositely mark the sites of beneficial mutations, and even turn them into recombination hotspots for a few millennia, to keep the party going. Hotspots may even arise randomly and spontaneously, as true, selectable epi-mutations. 

A Problem With Mutation Hotspots on the DNA Strand

The downside of all this is that even in an adaptive hotspot, most mutations will still be harmful, leading to the possibility of "hitchhiker" genetic diseases that cannot be efficiently selected against because they are sheltered in a hotspot. Cystic fibrosis may be such a disease, and as the hitchhiker mechanism would predict, it is caused by many different mutations, not just one. It would be a syndrome defined by the overlap of a vital structural gene and a hotspot, not by a single DNA mutation. I imagine hotspots to be much more extended along the DNA than a classic point mutation.

It is tempting to suppose that the methylation islands found on DNA are these hotspots, but the scanty evidence available so far is that methylation suppresses recombination hotspots, which are generally defined non-epigenetically, by the base-pair sequence.

Mental Illness In Evolution 

The human brain has undergone rapid, recent evolutionary expansion, presumably due to intense selection, presumably unmasking many deleterious mutations affecting brain development that were formerly silent. Since the brain is the organ of behavior, we expect almost all these mutations to indirectly affect behavior for the worse. Does that explain mental illness?

Mental illnesses are not random, but cluster into definable syndromes. My reading suggests the existence of three such syndromes: schizoid, depressive, and anxious. My theory is that each is defined by a different recombinant hot spot, as in the case of cystic fibrosis, and may even correspond to the three recently-evolved association cortices of the human brain, namely parietal, prefrontal, and temporal, respectively. 

How Mental Illness Could Be Beneficial 

The drama of mental illness would derive from a communication role in warning nearby relatives that they may be harbouring a bad hotspot, causing them to find it and cool it by wholly unconscious processes. Mental illness would then be the push-back against the hotspots driving human brain evolution, keeping them in check and deleting them as soon as they are no longer pulling their weight fitness-wise. The variations in the symptoms of mental illness would encode the information necessary to find the particular hot spot afflicting a particular family.

A Possible Mechanism

Now all we need is a communication link from brain to gonads. The sperm are produced by two rounds of meiosis and one of mitosis from the stem-like, perpetually self-renewing spermatogonia, which sit just outside the blood-testes barrier and are therefore exposed to all blood-borne hormones. These cells are known to have receptors for the hypothalamic hormone orexin A, as well as many other receptors for signalling molecules that do or could plausibly originate in the brain as does orexin A. Orexin A is lipophilic and rapidly crosses the blood-brain barrier by diffusion. Some of the other receptors are:

• retinoic acid receptor α
• glial cell-derived neurotrophic factor (GDNF) receptor
• CB2 (cannabinoid type 2) receptor
• p75 (For nerve growth factor, NGF)
• kisspeptin receptor.

PS: for brevity, I left out mention of three sub-functions necessary to the pathway: an intracellular gonadal process transducing receptor activation into germ line-heritable epigenetic changes, a process for exaggerating the effects of bad mutations into signals for purposes of interpersonal communication, and a process of decoding the communication in the brains of the recipients.

Photo by Charlotte Noelle on Unsplash

#5. Why We Dream [neuroscience]

NE

Red, theory; black, fact

The Conjunction of Jupiter and Venus

We Dream Because We Learn

Operant conditioning is the learning process at the root of all voluntary behaviour. The process was discovered in lab animals such as pigeons by B.F. Skinner in the 1950s and can briefly be stated as "If the ends are achieved, the means will be repeated." (Gandhi said something similar about revolutionary governments.)

Learning in the Produce Isle

Operant conditioning is just trial-and-error, like evolution itself, only faster. Notice how it must begin: with trying moves randomly--behavioral mutations. However, the process is not really random like a DNA mutation.  Clearly, common sense plays a role in getting the self-sticky polyethylene bag open for the first time, but any STEM-educated person will want to know just what this "common sense" is and how you would program it. Ideally, you want the  creativity and genius of pure randomness, AND the assurance of not doing anything crazy or even lethal just because some random-move generator suggested it. You vet those suggestions.

How Dreams Help Learning

That, in a nutshell, is dreaming: vetting random moves against our accumulated better judgment to see if they are safe--stocking the brain with pre-vetted random moves for use the next day when we are stuck. This is why the emotions associated with dreaming are more often unpleasant than pleasant: there are more ways to go wrong than to go right. The vetting is best done in advance (e.g., while we sleep) because there's no time in the heat of the action the next day, and trial-and-error with certified-safe "random" moves is already time-consuming without having to do the vetting on the spot as well.  

A Possible Neurobiological Mechanism

Dreams are loosely associated with brain electrical events called "PGO waves," which begin with a burst of action potentials ("nerve impulses") in a few small brainstem neuron clusters, then spread to the visual thalamus, then to the primary visual cortex. I theorize that each PGO wave creates a new random move that is installed by default in memory in cerebral cortex, and is then tested in the inner theatre of dreaming to see what the consequences would be. In the event of a disaster foreseen, the move would be scrubbed from memory, or better yet, added as a "don't do" to the store of accumulated wisdom. Repeat all night.

If memory is organized like an AI knowledge base, then each random move would actually be a connection from a randomly-selected but known stimulus to a randomly-selected but known response, amounting to adding a novel if-then rule to the knowledge base.

Support For a Requirement for Vetting 

In "Evolution in Four Dimensions" [1st ed.] Jablonka and Lamb make the point that epigenetic, cultural, and symbolic processes can come up with something much better than purely random mutations: variation that has been subjected to a variety of screening processes.

An Observation and an Exegesis

Oddly, my nightmares happen just after a turn of good fortune for me. However, in our evolutionary past, my kind of good fortune may have meant bad fortune for someone else, and that someone else will now be highly motivated to kill me in my sleep. Unless I have a nightmare and thus sleep poorly or with comforting others. The dream that warned the Wise Men not to return to Herod may have been just such a nightmare, which they were wise enough to interpret correctly. The content was probably not an angelic vision, but more like Ezekiel's valley of dry bones vision in reverse.

#4. My First Theory of Everything (TOE) [physics]

PH

Red, theory; black, fact

Detail of a mural by Barbara Vermer

Alocia and Anaevia

Can you make a case for the existence of absolute space and even suggest that space is some kind of condensate (e.g., a crystal)? The divide-and-conquer strategy that has served us so well in science suggests that the next step is to conceptually take this condensate apart into particles. The first question that arises is whether these particles are themselves situated in an older, larger embedding space, or come directly out of spacelessness (i.e., a strange, hypothetical early universe that I call "Alocia," my best Latin for "domain of no space." Going even further back, there would have been "Anaevia," "domain of no time." Reasoning without time seems even trickier than reasoning without space.)

What came before space?

The expansion of our universe suggests that the original, catastrophic condensation event, the big bang, was followed by further, slower accretion that continues to this day. However, the resulting expansion of space is uniform throughout its volume, which would be impossible if the incoming particles had to obey the rules of some pre-existing space. If there were a pre-existing space, incoming particles could only add to the exterior surface of the huge condensate in which we all presumably live, and could never access the interior unless our universe were not only embedded in a 4-space, but hyper-pizza-shaped as well. The latter is unlikely because self-attraction of the constituent particles would crumple any hyper-pizza-shaped universe into a hypersphere in short order. (Unless it spins?) Conclusion: the particles making up space probably have no spatial properties themselves, and bind together in a purely informational sense, governed by Hebb's rule. 

Hebb's rule was originally a neuroscience idea about how learning happens in the brain. My use of it here does not imply that a giant brain somehow underlies space. Rather, the evolutionary process that led to the human brain re-invented Hebb's rule as the most efficient way of acquiring spatial information. 

Hebb's rule pertains to signal sources: how could hypothetical space-forming particles come up with the endless supply of energy required by pumping out white noise, waves, etc., 24/7? Answer: these "particles" are the growing tips of time lines, that themselves grow by an energy-releasing accretion process. The chunks that accrete are variable in size or interrupted by voids, so timeline extension has entropy associated with it that represents the signals needed by Hebb's rule.

I am aware of all the space-bound terms in the previous paragraph (underlined), supposedly about goings-on in Alocia, the domain of no space; however, I am using models here as an aid to thought, a time-honored scientific technique.

Is cosmological expansion some kind of accretion?

I imagine that Alocia is home to large numbers of space-like condensates, with a size distribution favoring the microscopic, but with a long tail extending toward larger sizes. Our space grows because these mostly tiny pre-fab spaces are continually inserting themselves into it, as soon as their background signal pattern matches ours somewhere. This insertion process is probably more exothermic than any other process in existence. If the merging space happens to be one of the rarer, larger ones, the result would be a gamma ray burst bright enough to be observed at cosmological distances and generating enough pure energy to materialize all the cosmic rays we observe.

The boundary problem

I suspect that matter is annihilated when it reaches the edge of a space. This suggests that our space must be mostly closed to have accumulated significant amounts of matter. This agrees with Hawking's no-boundary hypothesis. The closure need not be perfect, however; indeed, that would be asking a lot of chance. Imperfections in the closure of our universe may take the form of pseudo-black holes: cavities in space that lack fields. If they subsequently acquire fields from the matter that happens to hit them, they could evolve to closely resemble super-massive black holes, and be responsible for nucleating galaxies.

Conclusions

• Spatial proximity follows from correlations among processes and does not cause them.
• Any independence of processes is primordial and decays progressively.
• The universe evolves through a succession of binding events, each creating a new property of matter, which can be interpreted as leftover entropy.
• Analysis in the present theoretical framework proceeds by declaring familiar concepts to be conflations of these properties, e.g., time = change + contrast + extent + unidirectional sequence; space = time + bidirectional sequence.

#3. Human Reproductive Control [population, engineering, evolutionary psychology]

PO   EN   EP

Red, theory; black, fact

Here, I go into detail about the human population controller introduced in the previous post.

The Relevance of Engineering 

I assume that this controller is a masterful piece of engineering, like everything in the natural (i.e., evolved) world, as Leonardo Da Vinci declared.

Application of Filter Theory

The way to build an ideal feed forward controller is the inverse plant method, where the controller contains the mathematical inverse of a mathematical model of the system to be controlled.  To derive the model, you take the Laplace transform of the system's impulse response function. For populations, a suitable impulse would be the instantaneous introduction of the smallest viable breeding population into an ideal habitat.

The Impulse Response Function 

What happens then is well known, as least in microbial life forms too simple to already have a controller: unrestrained, exponential population growth as per Malthus, with no end in sight.

This exponential curve is then the impulse response function we need, and its Laplace transform is simple: 1/(S - r), where S is complex frequency and r is the Malthusian constant, that is, percent population growth per year. 

The Inverse Model

The mathematical inverse is even simpler: S - r, which is multiplied by the sensor-error Laplace transform to get the controller output. Multiplication by S followed by subtraction of the zero-time signal is equivalent to differentiation in the time domain. The effect of S-domain subtraction and multiplication by a constant remain the same when transferred to the time domain.

In humanly engineered systems, a feedforward controller typically operates in conjunction with a downstream feedback controller.

  

The Sensor Signal

The level of the noise produced so copiously by small children is probably the signal that people unconsciously use to estimate birth rate, and the wailing and long faces following a death probably serve the same purpose for estimating death rate.  My married older brother once showed me the developmental time course of child noise in the air with his hand, and it looked like an EPSP, the response of a neuron to an incoming action potential. The EPSP is the convolution kernel by which a neuron decodes a rate code. This suggests that the differentiation operation is telescoped into the sensing operation.

#2. The Iatrogenic Conflicts of the Twentieth Century [population, engineering]

PO   EN

Red, theory; black, fact

Center: a centrifugal speed governor that would have been familiar in 1914. The Steam Museum, Kingston, Ontario

Medical Advances During a Turbulent Century

In 1911, the anti-syphilis drug salvarsan, invented by Paul Ehrlich, became widely available to the public, at a time when this disease was cutting a wide swath of morbidity and mortality. Three years later, World War I broke out.

In 1937, sulfa drugs, the first effective treatment for tuberculosis, became available to the public. Two years later, World War II broke out.

In 1945, both penicillin and streptomycin became available to the public, followed in short order by the first mass vaccinations, notably against smallpox. In that decade (1945-1955), the Cold War between the United States and the Soviet Union began. That one nearly finished us in 1962, the year of the Cuba Missile Crisis, when a nuclear WW III was narrowly averted.

A Possible Mechanism 

In the human brain, there may be a wholly unconscious controller for population density with a feedback delay of some two to four years, that answers every sudden downtick in the death rate with a brutal, reflexive uptick. Recently, these downticks in the death rate have been due to advances in medicine, hence my title for this post. "Iatrogenic" means roughly "caused by doctors."

Supporting Evidence

Moreover, last year I noted that the headlines were all about ISIS, an unusually disruptive phenomenon of the Muslim world. I then checked to see what the main preoccupation of the headline-writers had been exactly four years previously. This seemed to be the Arab Spring, when many old governments in the Arab world were being thrown off. I concluded that these regimes had somehow been suppressing population growth.

An Engineering Model

If this controller is real, it should be just as analyzable as Watt's steam-engine governor, using standard engineering approaches. If it has a significant feedback delay, then a perturbation sufficiently rich in high-frequency harmonics (i.e., sufficiently sudden) should drive it briefly into a damped oscillation.

Evidence for the Engineering Model

In support of these conclusions, here are the US Census Bureau statistics on the percent growth rate of the human population for the 20th century, international yearly figures, aggregated to "World," and extended back to 1900 with decade-wise World data from the historical estimates table. At roughly the end of WW II, there is a huge jump in the growth rate followed by a sharp drop bottoming at 1960, followed by another sharp peak at 1962, followed by a leveling off superimposed on a gradual decline, the latter possibly due to increasing absolute numbers. This time series could be construed as showing a damped oscillation. See below.

The historical global population growth rate scaled to population.

The surmise that the post-1964 decline in the plot would disappear if corrected for changing absolute numbers is confirmed by calculation based on US Census Bureau data. See below. Furthermore, the plot shown below appears to level off at 78 million new people per year, which is probably the upper trigger level for the controller. There is probably no formal lower trigger level, making this controller asymmetric. Oscillation begins well before this level is reached, however, indicating the possible presence of a differential control term. 

Other Features of the Data

The sharp upstroke in growth rate that occurs at 1980 may be due to the eradication of smallpox over the decade 1967-1977. The downturn after 1988 was probably due to the AIDS pandemic. The data are coarse-grained before 1950 and do not show the upstrokes in 1911-1914 and 1937-1939 that I would have predicted from the two world wars.

World population growth rates in persons per year with no scaling. Note the reaction in 1960.

Mechanism of the Putative Damped Oscillation

A scan of historical events for the period 1954-1960 turned up nothing notable except in 1957, the year the down-dip anomaly began. That year saw a flurry of atmospheric nuclear bomb testing, rocket development, and regime changes. Racial integration began in the USA. The dominant sentiment driving all these changes may have been: “We gotta protect the kids.” Of which there were quite a few. Perhaps the downturn in population growth lasted until parental concerns about security were allayed. In general, how does one provide security, universally desired but universally elusive? The matter may be complex and demand a formal science of security.

Had the issues simmering below the surface been different, the dominant sentiment may have been different, but the population growth curve reversal would have looked the same, being due to a child-driven loss of tolerance for problems previously tolerated.

#1. The Origin of the Eukaryotes [evolution]

EV

Red, theory; black, fact

A fossil (oncoid or stromatolite) of a colony of prokaryotes. Photographed in situ.

The eukaryotic cell may have arisen from a clonal array of prokaryotes that selectively lost some of its internal partition walls while following the colony path to complexity. The remaining partitions gave rise to the internal membrane systems of present-day eukaryotes. Those prokaryote colonists specializing in chemiosmotic processes such as oxidative phosphorylation and photosynthesis could not lose any of their delimiting walls because of the need to maintain concentration gradients, so they remain bacterium-like in morphology to this day. This is an alternative to the phagocytotic theory of the origin of mitochondria and chloroplasts. Modern blue-green algae genetically resemble the DNA in chloroplasts, and modern aerobic bacteria have genetic resemblances to the DNA in mitochondria, but this is not necessarily differential support for the phagocytosis theory. The resemblances can be accounted for by convergent evolution or by the existence of an ancestor common to the modern organisms and the ancient colony formers I suppose here.

These prokaryote colonies would have originally reproduced by sporulation, not mitosis, which would have come later. The "spores" would be actively-metabolizing prokaryotes and before growing into further colonies, would be subject to natural selection. In the spore phase, the rapid evolvability of typical prokaryotes would have been recovered, allowing the formation of large, slow-growing colonies without sacrifice of the high evolvability of the original solitary prokaryotes. Modern-day eukaryotes often secrete tiny bodies called exosomes containing all the macromolecules of life. Exosomes may be the evolutionary vestige of the sporulation phase of the original eukaryotes.