Presumably, it depends a lot on what the gene does. If it affects how your bones grow during childhood, and you’re now an adult, then you’re out of luck. If it produces a protein that has effects in the present, is easy to synthesize and deliver to the body where it matters, then it’s straightforward. (For example, if you want to digest lactose as an adult and lack the right genes, you can buy lactase pills apparently for 10¢.)
I’d also say that the complexity of the phenomenon may be very different from the complexity and difficulty of the cure: e.g. if you had some broken enzyme that caused your body to waste half of some essential vitamin, the consequences to your body might be very complex, but the solution might be to just take a vitamin supplement. At any rate, Wiki says that there are over 6000 genetic disorders, and that over 600 are treatable. The citation on the latter describes a database of known treatments for genetic disorders, and has some interesting numbers:
Enzyme replacement therapy (ERT) is available for 28 disorders. [...] Supplements are important in the treatment of 175 disorders [...] Medications, vaccinations, and blood products play a role in the management of 328 disorders. This includes 154 medications, 3 vaccines, and 9 different blood products.
Regarding the FNSS genes. For DEC2 in particular, it’s the interaction with orexin that makes the difference (the second DEC2 paper showed that an orexin receptor antagonist turned off the short-sleeper effect), and the orexin producers and receptors are all neurons in the brain. And ADRB1, NPSR1, and GRM1 all affect some kind of wakefulness-related receptor (it’s the R in all their names), which I expect are also in the brain. Delivering to the brain is more delicate than to the stomach, but it’s certainly doable.
My impression is that, by trying out different chemicals, you can hope to find one that binds to the receptor and either increases or decreases the activity of it (an “agonist” or “antagonist”) and ideally doesn’t bind to anything else; Ying-Hui said something along those lines. That’s roughly the extent of my knowledge.
I have an undergraduate degree in Neuroscience and I am very skeptical that such a drug can be found. Can’t talk to these specific genes in particular but genes are often turned on in different ways and in different parts of the brain, and lead to different effects based on which genes are turned on or off with them. Now because of the gene interaction in the background, the same receptor can cause a reverse effect when activated in one part of the brain or another. Additionally, each neurotransmitter has upwards of 20 different receptors in the brain. Also, every single synapse has multiple different receptors.
Drugs on the other hand hit all the receptors of a certain type in all of the brain. It’s a very indiscriminant effect. The diseases that medications seem to be capable of fixing are diseases that lead to a brain-wide shortage of a neurotransmitter, which are fixed by prescribing the transmitter or a medication that causes its recycling and reuptake (like levo-dopa for parkinson’s).
I’ve head a neuroscientist say once that treating disease with medication is like “fixing a car by pouring oil indiscriminantly under the hood,” and I agree. One example for that is SSRIs for depression. Serotonin does a lot of things in the brain - it also has an important role in motor functions. SSRIs help depression, but the effect isn’t very direct (people describe having some additional energy, not necessarily being ‘cured’) and has many, many side effects because they also affect all the other serotonin concentrations all over the brain.
Even when compared to mood control, sleep is also a very delicate, very carefully-orchestrated process in the brain. It’s controlled by similar centres as breathing, heart rate, and balance. Sure there are some rare genes that contribute to less sleep but I doubt you’ll find a drug that will not have severe side effects.
On a different note—I haven’t read her studies in particular but the main reason I left neuroscience was because the standard practices, especially in human and animal research, seemed to me so lacking. The recruitment process which you mentioned alone can be extremely biased, and is extremely hard to control for. The sample sizes are also always quite small. I wouldn’t be surprised if this group is skewed towards top 1/300th of people with this gene, and that they have numerous other genes and environmental factors that makes them more ‘protected’ from deprivation but also more likely to reach recruitment for this type of study.
TL;DR gene expression is tightly controlled over time and space and drugs are not. This is especially true for sleep. I am skeptic drugs will work at this fine scale since no current drugs do.
Presumably, it depends a lot on what the gene does. If it affects how your bones grow during childhood, and you’re now an adult, then you’re out of luck. If it produces a protein that has effects in the present, is easy to synthesize and deliver to the body where it matters, then it’s straightforward. (For example, if you want to digest lactose as an adult and lack the right genes, you can buy lactase pills apparently for 10¢.)
I’d also say that the complexity of the phenomenon may be very different from the complexity and difficulty of the cure: e.g. if you had some broken enzyme that caused your body to waste half of some essential vitamin, the consequences to your body might be very complex, but the solution might be to just take a vitamin supplement. At any rate, Wiki says that there are over 6000 genetic disorders, and that over 600 are treatable. The citation on the latter describes a database of known treatments for genetic disorders, and has some interesting numbers:
Regarding the FNSS genes. For DEC2 in particular, it’s the interaction with orexin that makes the difference (the second DEC2 paper showed that an orexin receptor antagonist turned off the short-sleeper effect), and the orexin producers and receptors are all neurons in the brain. And ADRB1, NPSR1, and GRM1 all affect some kind of wakefulness-related receptor (it’s the R in all their names), which I expect are also in the brain. Delivering to the brain is more delicate than to the stomach, but it’s certainly doable.
My impression is that, by trying out different chemicals, you can hope to find one that binds to the receptor and either increases or decreases the activity of it (an “agonist” or “antagonist”) and ideally doesn’t bind to anything else; Ying-Hui said something along those lines. That’s roughly the extent of my knowledge.
I have an undergraduate degree in Neuroscience and I am very skeptical that such a drug can be found. Can’t talk to these specific genes in particular but genes are often turned on in different ways and in different parts of the brain, and lead to different effects based on which genes are turned on or off with them. Now because of the gene interaction in the background, the same receptor can cause a reverse effect when activated in one part of the brain or another. Additionally, each neurotransmitter has upwards of 20 different receptors in the brain. Also, every single synapse has multiple different receptors.
Drugs on the other hand hit all the receptors of a certain type in all of the brain. It’s a very indiscriminant effect. The diseases that medications seem to be capable of fixing are diseases that lead to a brain-wide shortage of a neurotransmitter, which are fixed by prescribing the transmitter or a medication that causes its recycling and reuptake (like levo-dopa for parkinson’s).
I’ve head a neuroscientist say once that treating disease with medication is like “fixing a car by pouring oil indiscriminantly under the hood,” and I agree. One example for that is SSRIs for depression. Serotonin does a lot of things in the brain - it also has an important role in motor functions. SSRIs help depression, but the effect isn’t very direct (people describe having some additional energy, not necessarily being ‘cured’) and has many, many side effects because they also affect all the other serotonin concentrations all over the brain.
Even when compared to mood control, sleep is also a very delicate, very carefully-orchestrated process in the brain. It’s controlled by similar centres as breathing, heart rate, and balance. Sure there are some rare genes that contribute to less sleep but I doubt you’ll find a drug that will not have severe side effects.
On a different note—I haven’t read her studies in particular but the main reason I left neuroscience was because the standard practices, especially in human and animal research, seemed to me so lacking. The recruitment process which you mentioned alone can be extremely biased, and is extremely hard to control for. The sample sizes are also always quite small. I wouldn’t be surprised if this group is skewed towards top 1/300th of people with this gene, and that they have numerous other genes and environmental factors that makes them more ‘protected’ from deprivation but also more likely to reach recruitment for this type of study.
TL;DR gene expression is tightly controlled over time and space and drugs are not. This is especially true for sleep. I am skeptic drugs will work at this fine scale since no current drugs do.