How can biochemical interventions be spatially localized, and why is that problem important?
High vs low voltage has very different semantics at different places on a computer chip. In one spot, a high voltage might indicate a number is odd rather than even. In another spot, a high voltage might indicate a number is positive rather than negative. In another spot, it might indicate a jump instruction rather than an add.
Likewise, the same chemical species have very different semantics at different places in the human body. For example, high serotonin concentration along the digestive tract is a signal to digest, whereas high serotonin concentration in various parts of the brain signals… uh… other stuff. Similarly, acetylcholine is used as a neurotransmitter both at neuromuscular junctions and in the brain, and these have different semantics. More generally, IIUC neurotransmitters like dopamine, norepinephrine, or serotonin are released by neurons originating at multiple anatomically distinct little sub-organs in the brain. Each sub-organ projects to different places, and the same neurotransmitter probably has different semantics when different sub-organs project to different targets.
Yet most pharmaceutical interventions target one type of molecule, or one receptor, or what have you, approximately everywhere. Such an intervention is analogous to e.g. attempting to make every float in a computer’s memory positive by flipping the first bit in every block, but then as a side-effect also changing a bunch of jump instructions to add instructions because there was no way to localize the effect to float-containing memory locations.
Thus the question: how can biochemical interventions be localized, especially in general-purpose ways? I’ll throw out some ideas off the top of my head, but I’m interested to hear other peoples’ thoughts as well.
Some Methods
Natural Barriers
The blood-brain barrier springs to mind as one example. If a chemical has different semantics in the brain and outside, and one wishes to target outside the brain, then just use a drug which can’t cross the barrier.
Implant + Slow Transport/Fast Breakdown
One could put an implant in the right spot to release a drug, and then choose a drug which either isn’t transported quickly or breaks down before it can get very far (or both).
Notably, making some random molecule diffuse less quickly seems relatively tractable: one can just attach a bigger molecule to it. And there’s an absolutely enormous space of possibilities for what that bigger molecule could be, so it’s especially likely to be tractable.
Genetic Modification
Cells already need the ability to tell “where they are” in order for us to have anatomically distinct regions at all. So in principle, it should be possible to genetically modify cells to do something different, but gate the change on the cell being in a particular distinct anatomical region, so cells everywhere else do the same thing as before.
For adult genetic modifications, one would probably want to combine this method with something similar to the implant + slow transport/fast release method above. Adult genetic modifications usually don’t hit every cell or even a majority of them, so an ideal use would be modifying some small percentage of cells to release a molecule which influences all the others. Slow diffusion/fast breakdown could then localize that molecule.
What Else?
I’m curious about other methods to localize biochemical interventions in the body, both speculative and already-existing.
How can biochemical interventions be spatially localized, and why is that problem important?
High vs low voltage has very different semantics at different places on a computer chip. In one spot, a high voltage might indicate a number is odd rather than even. In another spot, a high voltage might indicate a number is positive rather than negative. In another spot, it might indicate a jump instruction rather than an add.
Likewise, the same chemical species have very different semantics at different places in the human body. For example, high serotonin concentration along the digestive tract is a signal to digest, whereas high serotonin concentration in various parts of the brain signals… uh… other stuff. Similarly, acetylcholine is used as a neurotransmitter both at neuromuscular junctions and in the brain, and these have different semantics. More generally, IIUC neurotransmitters like dopamine, norepinephrine, or serotonin are released by neurons originating at multiple anatomically distinct little sub-organs in the brain. Each sub-organ projects to different places, and the same neurotransmitter probably has different semantics when different sub-organs project to different targets.
Yet most pharmaceutical interventions target one type of molecule, or one receptor, or what have you, approximately everywhere. Such an intervention is analogous to e.g. attempting to make every float in a computer’s memory positive by flipping the first bit in every block, but then as a side-effect also changing a bunch of jump instructions to add instructions because there was no way to localize the effect to float-containing memory locations.
Thus the question: how can biochemical interventions be localized, especially in general-purpose ways? I’ll throw out some ideas off the top of my head, but I’m interested to hear other peoples’ thoughts as well.
Some Methods
Natural Barriers
The blood-brain barrier springs to mind as one example. If a chemical has different semantics in the brain and outside, and one wishes to target outside the brain, then just use a drug which can’t cross the barrier.
Implant + Slow Transport/Fast Breakdown
One could put an implant in the right spot to release a drug, and then choose a drug which either isn’t transported quickly or breaks down before it can get very far (or both).
Notably, making some random molecule diffuse less quickly seems relatively tractable: one can just attach a bigger molecule to it. And there’s an absolutely enormous space of possibilities for what that bigger molecule could be, so it’s especially likely to be tractable.
Genetic Modification
Cells already need the ability to tell “where they are” in order for us to have anatomically distinct regions at all. So in principle, it should be possible to genetically modify cells to do something different, but gate the change on the cell being in a particular distinct anatomical region, so cells everywhere else do the same thing as before.
For adult genetic modifications, one would probably want to combine this method with something similar to the implant + slow transport/fast release method above. Adult genetic modifications usually don’t hit every cell or even a majority of them, so an ideal use would be modifying some small percentage of cells to release a molecule which influences all the others. Slow diffusion/fast breakdown could then localize that molecule.
What Else?
I’m curious about other methods to localize biochemical interventions in the body, both speculative and already-existing.