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Interesting information... it prompted me to do more research. According to wikipedia, Vitamin B-9 is broken down by our bodies into a family of compounds call

by ddxxdd 4y ago

Interesting information... it prompted me to do more research. According to wikipedia, Vitamin B-9 is broken down by our bodies into a family of compounds called "THF", which: 1. Help synthesize DNA, 2. Help repair/modify DNA, 3. Help create the amino acid "Methionine", which is a precursor to other amino acids, and is thus important for the synthesis of many proteins inside the body, 4. Activate Vitamin B12. A deficiency in Vitamin B-9 can lead to a loss of appetite, weakness, heart palpitations, headaches, irritability, and anemia. Also interesting to note that a deficiency in Vitamin B-12 will cause the body to overcompensate and convert a large portion of Vitamin B-9 into the form that metabolizes Vitamin B12, which leads to a condition that mimics a deficiency of Vitamin B9. One of these days, when I have enough free time, I want to develop a particle-level simulation of the human body, so that medical students, doctors, and curious laymen can see these processes in action on their personal computers. If I combine that with an affordable at-home blood test/diagnostic system, we will have a mechanism to bring affordable healthcare to every single person in the country. And perhaps a reliable method to find the true cause of a patient's depression, before prescribing them SSRI's or other psychiatric drugs.

trentgreene 4y ago
If you ever want someone else to work with you on that, I atleast would be very interested
- ivoras 4y ago
  ... and my axe!
heavyset_go 4y ago
The compound is a key product in the methionine cycle[1], which is responsible for synthesizing neurotransmitters like serotonin. Poor methylation in this cycle can reduce synthesis of rate-limiting compounds in the cycle, thus limiting production of neurotransmitters, perhaps inducing symptoms of mental illness. Another product in this cycle is SAMe (S−adenosyl methionine), which has been marketed for decades as supplement for improving depression. [1] https://www.creative-proteomics.com/services/methionine-cycle-analysis-service.htm https://www.creative-proteomics.com/services/methionine-cycl...
bglazer 4y ago
Curious what you mean by “particle level”? Like simulating every molecule in the body?
- ddxxdd 4y ago
  At this time, I mean every hormone and protein flowing in the bloodstream, along with the state of every single cell. Essentially, enough detail to get a list of symptoms and bodily sensations, and predict the outcome of any potential blood test or urinalysis. Or, alternatively, enough detail to take the results of a blood test/urinalysis, and predict the state of every single tissue in the body.
  - heavyset_go 4y ago
    This is one of those hard problems in computing and medicine. Accurately simulating a neuron, for example, or other cells is beyond our capabilities. We have a difficult time even simulating individual receptors themselves on cells, which includes accurately predicting and simulating ligand binding on proteins.
  - PeterisP 4y ago
    It's something way beyond our current capabilities. There's some interesting work on "organs on a chip" e.g. arrays of microfluidic cell cultures that allows some experimentation on a combination of a few types of tissue modeling an organ or some aspect of it, but even that's already pushing the state of art and not fully mature at the moment; doing something similar for many (much less all or most) organs is something that doesn't work yet; and these "organs on a chip" are useful because pure simulation is even less mature and is unable to do what these cell cultures can. The goal you state is interesting, relevant, and potentially achievable, but it's still some decades away.
    - heavyset_go 4y ago
      Tangential to these are organoids[1] that emulate organs at much smaller scales, which I thought was cool. [1] https://en.wikipedia.org/wiki/Organoid https://en.wikipedia.org/wiki/Organoid
arthurofbabylon 4y ago
I’m not sure what you’re working on now - but the particle-level simulation seems exceptionally worthwhile to humanity and maybe uniquely suited to your skill and enthusiasm.
elcritch 4y ago
> One of these days, when I have enough free time, I want to develop a particle-level simulation of the human body, so that medical students, doctors, and curious laymen can see these processes in action on their personal computers. Likely you wouldn't need/want a particle level simulation, but a kinetics level model. Just with kinetics you could draw simulations of "particle concentrations" or other fun things to show medical students, etc, but without the need to simulate the actual chemicals. Though eventually hopefully we could do that too! The AlphaFold breakthrough is a huge advance toward that IMHO. > If I combine that with an affordable at-home blood test/diagnostic system, we will have a mechanism to bring affordable healthcare to every single person in the country. And perhaps a reliable method to find the true cause of a patient's depression, before prescribing them SSRI's or other psychiatric drugs. Just getting all the kinetics together would be amazing. You could essentially do what you're talking about of calculating most likely causes (not just correlations). Though brain chemistry != entirety of depression or whatnot. Still just getting even the top 20 chemical cycles mapped from blood tests could be pretty awesome and help bring light to a huge range of conditions. In my opinion, medicine currently is at a 1.0-1.5 order effects level. As in we can diagnose first order ailments pretty well. But second order effects? Not really, though I said 1.5 in that medical researchers and doctors are slowly figuring out some limited second order effects, like "X medicine with Y gene" or "X medicine with Y medicine" can have good or bad effects. We're certainly not talking about 3rd order effects.. We have the math, we have the statistics, but it's just hard maths and stats.
- operator-name 4y ago
  Sadly even a kinetics level simulation for anything remotely complex is far beyond what current compute is capable of. Even simplified models of basic biological processes are immensity complex, and still potentially incomplete. Just as neural networks do not even attempt to reach the level of molecules, (practical) models must necessarily exist at a much higher abstraction. Although alphafold is a breakthrough, this is less optimisation, more chaos theory.
  - ddxxdd 4y ago
    I'm not going to try to predict the shape of a protein from a chain of amino acids. I'm not going to try to predict the behavior of a human cell from Schrodinger's equation. My project's scope is more along the lines of: 1. Taking a look at Roche's list of all biochemical pathways in the human body[0]. 2. Creating a 3D model of a human body, assuming that all the molecules in the body interact only in the way that the chart prescribes. 3. Create a database of symptoms and sensations in the body, and use the 3D model to determine all the possible ways that the biochemical pathways could go awry in order to create the ailment. The way I envision it, the model is simply going after low-hanging fruit. [0] http://biochemical-pathways.com/#/map/1 http://biochemical-pathways.com/#/map/1
spangry 4y ago
Number 3 is very interesting - Methionine is a crucial precursor to producing glutathione, the body's "master antioxidant". If the inflammation / oxidation hypothesis of depression that I'm spruiking is correct, then B-9 supplementation may help alleviate depression by increase synthesis of glutathione which is turn would reduce the level of free-radical caused neuro-inflammation. I'm all for your particle-level simulation of the human body, I've had thoughts along similar lines (but unfortunately lack the skills and knowledge to implementation something like this).

by ddxxdd 4y ago

trentgreene 4y ago

If you ever want someone else to work with you on that, I atleast would be very interested

ivoras 4y ago
... and my axe!

heavyset_go 4y ago

The compound is a key product in the methionine cycle[1], which is responsible for synthesizing neurotransmitters like serotonin. Poor methylation in this cycle can reduce synthesis of rate-limiting compounds in the cycle, thus limiting production of neurotransmitters, perhaps inducing symptoms of mental illness. Another product in this cycle is SAMe (S−adenosyl methionine), which has been marketed for decades as supplement for improving depression. [1] https://www.creative-proteomics.com/services/methionine-cycle-analysis-service.htm https://www.creative-proteomics.com/services/methionine-cycl...

bglazer 4y ago

Curious what you mean by “particle level”? Like simulating every molecule in the body?

ddxxdd 4y ago
At this time, I mean every hormone and protein flowing in the bloodstream, along with the state of every single cell. Essentially, enough detail to get a list of symptoms and bodily sensations, and predict the outcome of any potential blood test or urinalysis. Or, alternatively, enough detail to take the results of a blood test/urinalysis, and predict the state of every single tissue in the body.
- heavyset_go 4y ago
  This is one of those hard problems in computing and medicine. Accurately simulating a neuron, for example, or other cells is beyond our capabilities. We have a difficult time even simulating individual receptors themselves on cells, which includes accurately predicting and simulating ligand binding on proteins.
- PeterisP 4y ago
  It's something way beyond our current capabilities. There's some interesting work on "organs on a chip" e.g. arrays of microfluidic cell cultures that allows some experimentation on a combination of a few types of tissue modeling an organ or some aspect of it, but even that's already pushing the state of art and not fully mature at the moment; doing something similar for many (much less all or most) organs is something that doesn't work yet; and these "organs on a chip" are useful because pure simulation is even less mature and is unable to do what these cell cultures can. The goal you state is interesting, relevant, and potentially achievable, but it's still some decades away.
  - heavyset_go 4y ago
    Tangential to these are organoids[1] that emulate organs at much smaller scales, which I thought was cool. [1] https://en.wikipedia.org/wiki/Organoid https://en.wikipedia.org/wiki/Organoid

arthurofbabylon 4y ago

I’m not sure what you’re working on now - but the particle-level simulation seems exceptionally worthwhile to humanity and maybe uniquely suited to your skill and enthusiasm.

elcritch 4y ago

> One of these days, when I have enough free time, I want to develop a particle-level simulation of the human body, so that medical students, doctors, and curious laymen can see these processes in action on their personal computers. Likely you wouldn't need/want a particle level simulation, but a kinetics level model. Just with kinetics you could draw simulations of "particle concentrations" or other fun things to show medical students, etc, but without the need to simulate the actual chemicals. Though eventually hopefully we could do that too! The AlphaFold breakthrough is a huge advance toward that IMHO. > If I combine that with an affordable at-home blood test/diagnostic system, we will have a mechanism to bring affordable healthcare to every single person in the country. And perhaps a reliable method to find the true cause of a patient's depression, before prescribing them SSRI's or other psychiatric drugs. Just getting all the kinetics together would be amazing. You could essentially do what you're talking about of calculating most likely causes (not just correlations). Though brain chemistry != entirety of depression or whatnot. Still just getting even the top 20 chemical cycles mapped from blood tests could be pretty awesome and help bring light to a huge range of conditions. In my opinion, medicine currently is at a 1.0-1.5 order effects level. As in we can diagnose first order ailments pretty well. But second order effects? Not really, though I said 1.5 in that medical researchers and doctors are slowly figuring out some limited second order effects, like "X medicine with Y gene" or "X medicine with Y medicine" can have good or bad effects. We're certainly not talking about 3rd order effects.. We have the math, we have the statistics, but it's just hard maths and stats.

operator-name 4y ago
Sadly even a kinetics level simulation for anything remotely complex is far beyond what current compute is capable of. Even simplified models of basic biological processes are immensity complex, and still potentially incomplete. Just as neural networks do not even attempt to reach the level of molecules, (practical) models must necessarily exist at a much higher abstraction. Although alphafold is a breakthrough, this is less optimisation, more chaos theory.
- ddxxdd 4y ago
  I'm not going to try to predict the shape of a protein from a chain of amino acids. I'm not going to try to predict the behavior of a human cell from Schrodinger's equation. My project's scope is more along the lines of: 1. Taking a look at Roche's list of all biochemical pathways in the human body[0]. 2. Creating a 3D model of a human body, assuming that all the molecules in the body interact only in the way that the chart prescribes. 3. Create a database of symptoms and sensations in the body, and use the 3D model to determine all the possible ways that the biochemical pathways could go awry in order to create the ailment. The way I envision it, the model is simply going after low-hanging fruit. [0] http://biochemical-pathways.com/#/map/1 http://biochemical-pathways.com/#/map/1

spangry 4y ago

Number 3 is very interesting - Methionine is a crucial precursor to producing glutathione, the body's "master antioxidant". If the inflammation / oxidation hypothesis of depression that I'm spruiking is correct, then B-9 supplementation may help alleviate depression by increase synthesis of glutathione which is turn would reduce the level of free-radical caused neuro-inflammation. I'm all for your particle-level simulation of the human body, I've had thoughts along similar lines (but unfortunately lack the skills and knowledge to implementation something like this).