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.
One silly sci-fi idea is this. You might have a few “trigger pills” which are smaller than a blood cell, and travel through the bloodstream. You can observe them travel through the body using medical imaging techniques (e.g. PET), and they are designed to be very observable.
You wait until one of them is at the right location, and send very precise x-rays at it from all directions. The x-ray intensity is 1(distance from pill)2. A mechanism in the trigger pill responds to this ionizing (or heating?), and it anchors to the location using a chemical glue or physical mechanisms (hooks, string, etc.).
Once the trigger pill is anchored in place, another drug can be taken which only activates when it contacts the trigger pill. (Which might activate yet another drug, if you really want to amplify the effect of this tiny trigger pill.)
This results is a ton of drug activity in that area, without needing invasive surgery.
If you want it to become a bigger and more permanent implant, you might make it grow over time (by adding another chemical), deliberately forming a blood clot. Medical imaging may make sure the trigger pill is in a small expendable blood vessel (you detect the pill moving slower with more twists and turns). It might be designed so that yet another chemical can cover it up or destroy it, in case you need to start over at a new location.
It might be radioactive if it’s trying to treat cancer.
It might be magnetically activated if you want real-time control of drug intensity.
Speaking of magnetically activating it, maybe even the anchoring is triggered by a magnetic field rather than x-rays. It won’t be aimed as precisely, so you can only have one trigger pill at a time, and may have to wait really long before it travels to the right area (the human body is pretty big compared to any small target).
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.
One silly sci-fi idea is this. You might have a few “trigger pills” which are smaller than a blood cell, and travel through the bloodstream. You can observe them travel through the body using medical imaging techniques (e.g. PET), and they are designed to be very observable.
You wait until one of them is at the right location, and send very precise x-rays at it from all directions. The x-ray intensity is 1(distance from pill)2. A mechanism in the trigger pill responds to this ionizing (or heating?), and it anchors to the location using a chemical glue or physical mechanisms (hooks, string, etc.).
Once the trigger pill is anchored in place, another drug can be taken which only activates when it contacts the trigger pill. (Which might activate yet another drug, if you really want to amplify the effect of this tiny trigger pill.)
This results is a ton of drug activity in that area, without needing invasive surgery.
If you want it to become a bigger and more permanent implant, you might make it grow over time (by adding another chemical), deliberately forming a blood clot. Medical imaging may make sure the trigger pill is in a small expendable blood vessel (you detect the pill moving slower with more twists and turns). It might be designed so that yet another chemical can cover it up or destroy it, in case you need to start over at a new location.
It might be radioactive if it’s trying to treat cancer.
It might be magnetically activated if you want real-time control of drug intensity.
Speaking of magnetically activating it, maybe even the anchoring is triggered by a magnetic field rather than x-rays. It won’t be aimed as precisely, so you can only have one trigger pill at a time, and may have to wait really long before it travels to the right area (the human body is pretty big compared to any small target).