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April 15 - July 10, 2024
SARS-COV2 stops the infected cell from secreting type 1 interferon.
most severe cases of SARS-COV2 infection, he found, occurred in patients—typically men—who lacked the ability to elicit a functional type 1 interferon signal after infection.
The pathogenicity of SARS-COV2, in short, perhaps lay precisely in its ability to dupe cells into believing that it is not pathogenic.
The war against the virus—as much as the virus itself—became an escalating crisis.
timing of the response—the impairment of early phase, followed by hyperactivity of the late phase, the main problem? We don’t know.
epistemology: how we know what we know.
We cannot know the unknown unknowns.
We look, we create, we imagine—but find only incomplete explanations for phenomena, even phenomena we may have (partially) discovered through our own work. We cannot inhabit their minds.
Covid exposed the humility that is required to cohabitate with these characters surrounding us.
I cannot think of a scientific moment that has revealed such deep and fundamental shortcomings in our knowledge of the biology of a system that we had thought we knew.
Cellular specialization and citizenship—the hallmarks of the cell biology of an organ—result in the profound “emergent” properties of human physiology—i.e.,
The heart, of all organs in the body, epitomizes belonging. We use the word “belong” to signify attachment, or love—and the heart has been the central signifier of that feeling for millennia
“The concept of a circuit of blood does not destroy, but rather advances […] medicine,”
cells of the heart “branch and intercommunicate, forming a continuum.”
citizenry of cells.
heart cells are connected to each other through minuscule molecular channels, called gap junctions.
designed to communicate with the next. Although many, they behave as one.
movement of ions—principally calcium—in and out of cells through specialized channels on the membranes of heart cells.
glial cells, the non-neuronal cells that support the function of the nerves)—ultimately
individual neuronal cells, with intricate, delicate anatomy, that reached out to connect with individual neuronal cells.
He argued that information traveled unidirectionally in a nerve.
Even that phrase—“drawing a conclusion”—illuminates the connection between thinking and drawing:
The ions stimulate the opening of more channels in the axon.
ion-sensitive ion channels are the linchpins in axonal conduction:
One chattering, thoughtful neuron has “spoken” to the next. The neuron’s two countermelodies are woven together in tandem, like a child’s chant: electrical, chemical, electrical, chemical, electrical.
synapse has the capacity not just to excite the neuron to fire—as
it can also be an inhibitory synapse, making the next neuron less prone to excitation. A single neuron can thus have positive inputs and negative inputs from other ne...
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Of all cells in the body, the neuron is, perhaps, the most subtle and the most magnificent.
we should imagine the neuron not just as a passive “wire” but as an active integrator.IV
not the stuff, but the stuffing of the brain.
they don’t generate electrical impulses,
These waves configure the wiring of the brain—rehearsing
“Cells that fire together, wire together.”)
It’s an odd phenomenon—our brains make connections in vast excess, and then we pare back the excess.
“The secret of learning is the systematic elimination of excess. We grow, mostly, by dying.”
For decades, the neuron sashayed down cell biology’s runway so glamorously that it hid the glial cell.
Neuronal signaling from one cell to the next instigates profound biochemical and metabolic changes in the recipient cell.
described depression as a “flaw in love.” But in medical terms, it was a problem with the regulation of neurotransmitters and their signals. A flaw in chemicals.
Paul believes that these proteins, which modify neuronal activity, are crucial to the slow signaling in neurons that regulate mood and emotional homeostasis.
BA25 was hyperactive in patients with recalcitrant depression,
chronic electrical stimulation of a neuronal circuit at high frequencies can depress its activity.
hormon—to impel, or to set some action into motion.
they impel the body to act as a whole.
“pan” (all) and “kreas”(flesh)—an organ of all flesh.
we generate excess, and then pare it back to restore normalcy.
We think of metabolism as a mechanism to generate energy. But flip it around, and it’s also a mechanism to generate waste.
pancreatic cell maintains metabolic constancy, the kidneys salt constancy. The liver maintains chemical constancy.
liver, pancreas, brain, and kidney are four of the principal organs of homeostasis.II
When those systems succeed, there is fixity. There is life.
Hiroshima provided proof that the human body possesses cells that continuously generate blood, not just in the moment, but for prolonged periods of time, through adulthood.
