#84. Next Niche [evolution]

Safdie’s Habitat 67 in Montreal 

Red, theory; black, fact

Evolutionarily, where did Homo sapiens come from and where are we going? The fossil evidence shows that we evolved from a wandering big-game hunter called Homo erectus. Where are we going? What shall be our next ecological niche? 

Reef former.

Examples of reef formers are the species of coral polyp that built the Great Barrier Reef in Australia. Think of such a structure transposed to a land environment and covered in solar panels like the leaves on a tree, and that, I think, is our distant future.

Multiple works of science fiction have predicted something like this, such as Asimov’s pre-collapse Trantor, or the world of JG Ballard’s “Build-Up.” 

However, a reef does not cover an entire planet as in those imaginings, only those places where all its necessities of life are available. The non-reef-forming descendants of H. sapiens would occupy some or all of the remaining land area.

Photo by philippe collard on Unsplash

#83. Ideas that May Become Posts [mostly evolutionary psychology]

[Quotes indicate metaphor.]

• Organized religion is a counter-adaptation to the anti-invasion adaptations of a neighboring, powerful country; one anti-invasion adaptation may be to weaken all neighboring countries. For the Abrahamic religions, that powerful but geographically vulnerable country would be ancient Egypt. For the Eastern religions, the powerful but vulnerable neighbor would be ancient China.

• People are "amphibians": each of us has a collectivist part existing in genetic superposition with an individualistic part. In systems that officially celebrate the former, the latter cannot be owned and must be pushed into the Jungian Shadow. And vice versa. In Freudian terms, the unacceptable wishes emerge in disguised form: religion in individual-celebrating systems, and hero worship in collective-celebrating systems.

• The longstanding debate in philosophy between rationalism and empiricism is a false dichotomy resulting from a narrow focus on one or the other of the two legs by which scientific knowledge advances: theory and experiment.

• If religion is the last protoscience, then the corresponding science that is to come could be called security science. 

• The incredible disunity of Protestantism could mean that Protestantism is the laboratory of Christianity.

• Science has to be for everyone.

• We don't have free will in the big things; we have free will in the little things. However, one of the little things can be "planting a seed" that may one day grow into one of those big things and be more to our liking than the big things we see now.

#82. Protein Batteries and Protein Misfolding Diseases [biochemistry]

Red, theory; black, fact

Last update: 24-14-2025

The commonest protein misfolding disease, Alzheimer’s, features an accumulation of insoluble proteins as amyloid plaques that damage neurons and lead to dementia and death. 

The amyloid precipitates from a solution of amyloid beta protein, which forms by a two-step proteolysis of amyloid precursor protein (APP), an integral membrane protein of neurons.

APP is thought to play a role in the initial stage of synaptic plasticity and contains a copper binding site.

Oxidation of the coordinated copper upon insertion of nascent APP in the plasma membrane could shift the coordination geometry of the copper ion from planar-triangular to pyramidal, with huge changes in the preferred bond angles. If the coordinating protein cannot accommodate these changes without input of activation energy, the result would be a “protein battery”: a protein carrying a metastable “charge” of conformational strain energy. A set mousetrap would be a familiar example of this. The local availability of this energy cache may be necessary to allow brief pre-and-postsynaptic electrical coincidences to be rapidly captured as preliminary synaptic morphological changes. The calcium-binding site next to the copper binding site (growth factor-like domain) may be the electric field sensor. Coincidence detection would involve same-molecule binding of APP molecules on opposite sides of the synaptic cleft, triggered by propagation of unleashed conformational changes from the copper site into the main extracellular domain, called the heparan-binding domain. (Better known parts of the coincidence detecting system are the NMDA receptor and CAM kinase II).

I propose that protein misfolding diseases of the brain are powered by a short circuiting of the APP energy caches, or analogous caches in proteins subserving other functions. <03-14-25: One of those other functions could be replenishing the supply of docked synaptic vesicles in response to a sudden increase in the average neuron firing rate. In that case, the relevant battery protein would be alpha synuclein, which is implicated in Parkinson’s Disease. Local energy caches are also present in humanly engineered electronic circuits, where they are called decoupling capacitors.>

The secretases implicated in Alzheimer’s etiology would serve to degrade the discharged APP molecules. Let us suppose that secretase alpha acts rapidly to clear action-potential-discharged APP that did not make a cross link, and secretase beta acts slowly to clear cross links. Secretase gamma would complete the cleavage in both cases. Secretase alpha would have a recognition site for discharged APPs and secretase beta would have an allosteric recognition site for cross links. Beta secretase action is known to release amyloid beta, the battery part of APP. I postulate that the stored energy in amyloid beta drives the polymerization process that leads to amyloid formation. This energy release would involve a conformational change, consistent with the finding that amyloid protein is misfolded. The conformational change could expose hydrophobic residues on the surface of the protein, an energy-requiring step that could lead directly to precipitation due to hydrophobic bonding among the amyloid beta molecules. This action is easier to imagine for the central hydrophobic domain of alpha synuclein, the immediate effect being not precipitation but pulling two arbitrary ligands on different alpha synuclein molecules into closer proximity for a faster reaction between them. The trigger appears to be phosphorylation of alpha synuclein, not electric field change.

By mischance, the soluble amyloid beta oligomers that form as intermediates along the amyloid-generating pathway are able to spoof APP cross links, thereby driving ectopic secretase beta activity and closing a feedback loop. This feedback leads to an out-of-control production of amyloid beta that produces Alzheimer’s disease.