7 ms·

Human body-on-chip platform could speed up drug testing

84 points by trott 6y ago

TravisSc6tt 6y ago
So they're basically trying to simulate humans? What a world we live in
- BurningFrog 6y ago
  Step by step, we are becoming obsolete...
  - xiphias2 6y ago
    Actually for drug research that's a good thing
hprotagonist 6y ago
If you can really, truly get liver-on-a-chip to work, it's going to positively change drug testing forever and will be the first huge win for tissue engineering. You can throw away animal models for tox screens forever, and that's great news. It will save vast amount of time and money. By using a much better proxy model for humans (slices aren't organs, they have different rheological characteristics and morphology, but they're a damn sight better than mice), you'll wash out candidates earlier and faster, and hopefully enrich the pipeline. Slowly but surely, and it's good to see steps in this direction.
- refurb 6y ago
  Meh. There are plenty of human cell line derived assays for things like membrane permeability, liver toxicity, etc. Those assays are super helpful, but don't replicate what happens in humans. They are good boxes to check, and can help weed out compounds early, but just because a compound passes the assay doesn't guarantee something weird won't pop up in humans.
  - kovek 6y ago
    Is it possible that these proxies you mention could weed out compounds incorrectly? For example, if we have a liver proxy that fails on drug A, is it possible that drug A will work fine in the human body provided that there’s a lot of other processes that could contribute to the liver?
    - refurb 6y ago
      Absolutely. That's the flip side of in vitro and animal testing. You might see a negative signal and stop development, only to find out that it can't be replicated in humans. The cell line assays replicate much of what happens in humans, but not all of it, in particular the interactions between different tissues. For example, a drug might be toxic in a liver assay because a reactive metabolite damages the cells. But in an actual human, you might never see those high of concentrations in the liver or there may be a process (like glutathione adducts) that deactivates the metabolite and prevents cell damage.
  - hprotagonist 6y ago
    right. i want to go beyond cell assays, i want high throughput organ slices that preserve important morphologies. it’s not a perfect model, but i think it’s a better proxy than a mouse.
- taffer 6y ago
  > It will save vast amount of time and money. And it will prevent much animal suffering.
econcon 6y ago
I've heard nearly any implant you put inside body has negative impact and this is also true for titanium implants which is seemingly inert and harmless metal. How many people their body with some industrial chip, I'll never use anything like this unless my life depends on it.
- wgrover 6y ago
  This isn't a chip for implanting inside the body; this is a microfluidic chip that replicates some body systems in the laboratory.
  - monkeydust 6y ago
    OK why the need for a physical chip, why not replicate in software?
    - anamexis 6y ago
      Because we can't effectively model the behavior of human tissue in software.
      - hprotagonist 6y ago
        by a long shot, too.
      - eximius 6y ago
        We can't even effectively model basic chemistry. We can't a priori tell you what color a chemical will be, much less many of its other properties.
    - fao_ 6y ago
      Look at how much energy and computer cycles they have to put into just for folding a single protein and then realise that scaling it up at our current level is basically impossible: https://foldingathome.org/ https://foldingathome.org/
    - 6y ago
dvt 6y ago
Does anyone have a layman-accessible explanation for how exactly this works? My last biology class was freshman year of college, but I find the "body-on-chip" startups incredibly interesting. I take it this is different than "growing" organs via stem cells?
- vikramkr 6y ago
  Basically, when you are growing organs or organoids (or 3d printing organs) with stem cells (which are used for organ on a chip too), you're actually trying to recreate the physical organ itself in it's original structure/function. You can imagine in the extreme the end result of trying to do this with a lung would be actually having a working lung that you could transplant into a person. Organ on a chip is less about making a lung, amd more about making a very controllable device that that has all the relevant behaviors and characteristics of a lung, so you can experiment with it. The end result of this might be a bunch of chips all connected to eachother with all sorts of tubes, and different cells grown in each tube with exact stimuli of all sorts being applied by an automated system. The goal wouldn't be to make a long you could put into a person. Rather, the goal would be to make something that, when you put a drug in through one of the tubes, would tell you exactly what would happen to the drug and how the lung of a real person would react if you were to give them the drug. The lines can get blurred, organoids on a chip, 3d printed organs used for research purposes, etc. But in general, (and you'll see this in how the different companies market themselves) growing organs is trying to get functional organs that could eliminate the need for a donor for an organ transplant, and organ on a chip is trying to get perfect research tools to eliminate the need for mice in research.
  - sanarothe 6y ago
    This reminds me very much of manufacturing quality testing, where you do initial DoE and validation builds to develop knowledge of the process. Eventually the knowledge of procc behavior at boundary conditions is known well enough that you can start to use alternative process monitoring approaches, like building a representative mockup of in-vitro conditions that represents the actual use conditions. It doesnt have to be the same vector, just the same eigenvector.
echelon 6y ago
We need to clone decephalized humans and livestock. With thousands of brainless bodies kept alive on life support, you have test subjects for a limitless number of experiments that would have never been possible before. You also create a never-ending O negative blood supply and organ harvesting program. It the case of decephalized animals, you also get cruelty free meat. And that's how you bootstrap the program and port it to the human model. There would be a lot of political pressure, but this would be a space-age jump in supporting fundamental biological research, supplying renewable body parts and tissues, and keeping us healthy and young. We need to do it. If I ever get Elon Musk money and power, I'm doing this instead of rockets.
- bollu 6y ago
  Interesting; I have never heard the word "decephalized" before --- in what literature in this used?
- encephaloner 6y ago
  >With thousands of brainless bodies kept alive on life support, you have test subjects for a limitless number of experiments that would have never been possible before. You also create a never-ending O negative blood supply and organ harvesting program. what society would ever produce decephalized humans when they could produce cephalized humans? a weak society that could not possibly adapt or grow. >It the case of decephalized animals, you also get cruelty free meat. only if you redefine cruelty to mean "what happens when bad things happen right in front of you". If a tree falls in a forest and no one hears... >And that's how you bootstrap the program and port it to the human model. of course, it's really no surprise. why are farmers less intelligent than hunter-gatherers? the process of domestication is self-imprinting. I think vegetarians really do have a point- not one that has to do with the cruelty of animals on an individual level, but with the very nature of domestication of animals itself. because the slippery slope of husbandry is ALWAYS eugenics. and the morality applied to animals always gets applied to humans given enough time. >There would be a lot of political pressure, but this would be a space-age jump in supporting fundamental biological research, supplying renewable body parts and tissues, and keeping us healthy and young. >We need to do it. >If I ever get Elon Musk money and power, I'm doing this instead of rockets. of course WE need to do it right? for millions of years humans lived and were forced to accept death, but THIS is the generation that we need to change by creating unholy abominations of our own kind. You are pathetically evil. I will patiently wait for you to die. Let me tell you who you are: "Many modern people, on the other hand, are disturbed by the prospect of physical deterioration and death, as is shown by the amount of effort they expend trying to maintain their physical condition, appearance and health. We argue that this is due to unfulfillment resulting from the fact that they have never put their physical powers to any practical use, have never gone through the power process using their bodies in a serious way. It is not the primitive man, who has used his body daily for practical purposes, who fears the deterioration of age, but the modern man, who has never had a practical use for his body beyond walking from his car to his house. It is the man whose need for the power process has been satisfied during his life who is best prepared to accept the end of that life."
deleted 6y ago
[deleted]

84 points by trott 6y ago

TravisSc6tt 6y ago

So they're basically trying to simulate humans? What a world we live in

BurningFrog 6y ago
Step by step, we are becoming obsolete...
- xiphias2 6y ago
  Actually for drug research that's a good thing

hprotagonist 6y ago

If you can really, truly get liver-on-a-chip to work, it's going to positively change drug testing forever and will be the first huge win for tissue engineering. You can throw away animal models for tox screens forever, and that's great news. It will save vast amount of time and money. By using a much better proxy model for humans (slices aren't organs, they have different rheological characteristics and morphology, but they're a damn sight better than mice), you'll wash out candidates earlier and faster, and hopefully enrich the pipeline. Slowly but surely, and it's good to see steps in this direction.

refurb 6y ago
Meh. There are plenty of human cell line derived assays for things like membrane permeability, liver toxicity, etc. Those assays are super helpful, but don't replicate what happens in humans. They are good boxes to check, and can help weed out compounds early, but just because a compound passes the assay doesn't guarantee something weird won't pop up in humans.
- kovek 6y ago
  Is it possible that these proxies you mention could weed out compounds incorrectly? For example, if we have a liver proxy that fails on drug A, is it possible that drug A will work fine in the human body provided that there’s a lot of other processes that could contribute to the liver?
  - refurb 6y ago
    Absolutely. That's the flip side of in vitro and animal testing. You might see a negative signal and stop development, only to find out that it can't be replicated in humans. The cell line assays replicate much of what happens in humans, but not all of it, in particular the interactions between different tissues. For example, a drug might be toxic in a liver assay because a reactive metabolite damages the cells. But in an actual human, you might never see those high of concentrations in the liver or there may be a process (like glutathione adducts) that deactivates the metabolite and prevents cell damage.
- hprotagonist 6y ago
  right. i want to go beyond cell assays, i want high throughput organ slices that preserve important morphologies. it’s not a perfect model, but i think it’s a better proxy than a mouse.
taffer 6y ago
> It will save vast amount of time and money. And it will prevent much animal suffering.

econcon 6y ago

I've heard nearly any implant you put inside body has negative impact and this is also true for titanium implants which is seemingly inert and harmless metal. How many people their body with some industrial chip, I'll never use anything like this unless my life depends on it.

wgrover 6y ago
This isn't a chip for implanting inside the body; this is a microfluidic chip that replicates some body systems in the laboratory.
- monkeydust 6y ago
  OK why the need for a physical chip, why not replicate in software?
  - anamexis 6y ago
    Because we can't effectively model the behavior of human tissue in software.
    - hprotagonist 6y ago
      by a long shot, too.
    - eximius 6y ago
      We can't even effectively model basic chemistry. We can't a priori tell you what color a chemical will be, much less many of its other properties.
  - fao_ 6y ago
    Look at how much energy and computer cycles they have to put into just for folding a single protein and then realise that scaling it up at our current level is basically impossible: https://foldingathome.org/ https://foldingathome.org/
  - 6y ago

dvt 6y ago

Does anyone have a layman-accessible explanation for how exactly this works? My last biology class was freshman year of college, but I find the "body-on-chip" startups incredibly interesting. I take it this is different than "growing" organs via stem cells?

vikramkr 6y ago
Basically, when you are growing organs or organoids (or 3d printing organs) with stem cells (which are used for organ on a chip too), you're actually trying to recreate the physical organ itself in it's original structure/function. You can imagine in the extreme the end result of trying to do this with a lung would be actually having a working lung that you could transplant into a person. Organ on a chip is less about making a lung, amd more about making a very controllable device that that has all the relevant behaviors and characteristics of a lung, so you can experiment with it. The end result of this might be a bunch of chips all connected to eachother with all sorts of tubes, and different cells grown in each tube with exact stimuli of all sorts being applied by an automated system. The goal wouldn't be to make a long you could put into a person. Rather, the goal would be to make something that, when you put a drug in through one of the tubes, would tell you exactly what would happen to the drug and how the lung of a real person would react if you were to give them the drug. The lines can get blurred, organoids on a chip, 3d printed organs used for research purposes, etc. But in general, (and you'll see this in how the different companies market themselves) growing organs is trying to get functional organs that could eliminate the need for a donor for an organ transplant, and organ on a chip is trying to get perfect research tools to eliminate the need for mice in research.
- sanarothe 6y ago
  This reminds me very much of manufacturing quality testing, where you do initial DoE and validation builds to develop knowledge of the process. Eventually the knowledge of procc behavior at boundary conditions is known well enough that you can start to use alternative process monitoring approaches, like building a representative mockup of in-vitro conditions that represents the actual use conditions. It doesnt have to be the same vector, just the same eigenvector.

echelon 6y ago

We need to clone decephalized humans and livestock. With thousands of brainless bodies kept alive on life support, you have test subjects for a limitless number of experiments that would have never been possible before. You also create a never-ending O negative blood supply and organ harvesting program. It the case of decephalized animals, you also get cruelty free meat. And that's how you bootstrap the program and port it to the human model. There would be a lot of political pressure, but this would be a space-age jump in supporting fundamental biological research, supplying renewable body parts and tissues, and keeping us healthy and young. We need to do it. If I ever get Elon Musk money and power, I'm doing this instead of rockets.

bollu 6y ago
Interesting; I have never heard the word "decephalized" before --- in what literature in this used?
encephaloner 6y ago
>With thousands of brainless bodies kept alive on life support, you have test subjects for a limitless number of experiments that would have never been possible before. You also create a never-ending O negative blood supply and organ harvesting program. what society would ever produce decephalized humans when they could produce cephalized humans? a weak society that could not possibly adapt or grow. >It the case of decephalized animals, you also get cruelty free meat. only if you redefine cruelty to mean "what happens when bad things happen right in front of you". If a tree falls in a forest and no one hears... >And that's how you bootstrap the program and port it to the human model. of course, it's really no surprise. why are farmers less intelligent than hunter-gatherers? the process of domestication is self-imprinting. I think vegetarians really do have a point- not one that has to do with the cruelty of animals on an individual level, but with the very nature of domestication of animals itself. because the slippery slope of husbandry is ALWAYS eugenics. and the morality applied to animals always gets applied to humans given enough time. >There would be a lot of political pressure, but this would be a space-age jump in supporting fundamental biological research, supplying renewable body parts and tissues, and keeping us healthy and young. >We need to do it. >If I ever get Elon Musk money and power, I'm doing this instead of rockets. of course WE need to do it right? for millions of years humans lived and were forced to accept death, but THIS is the generation that we need to change by creating unholy abominations of our own kind. You are pathetically evil. I will patiently wait for you to die. Let me tell you who you are: "Many modern people, on the other hand, are disturbed by the prospect of physical deterioration and death, as is shown by the amount of effort they expend trying to maintain their physical condition, appearance and health. We argue that this is due to unfulfillment resulting from the fact that they have never put their physical powers to any practical use, have never gone through the power process using their bodies in a serious way. It is not the primitive man, who has used his body daily for practical purposes, who fears the deterioration of age, but the modern man, who has never had a practical use for his body beyond walking from his car to his house. It is the man whose need for the power process has been satisfied during his life who is best prepared to accept the end of that life."

deleted 6y ago

[deleted]