Human body-on-chip platform could speed up drug testing | Hacker News Reader

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

europeanscientist.com

84 pointstrott38 comments

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.

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.

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?

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.

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.

> It will save vast amount of time and money.

And it will prevent much animal suffering.

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.

Interesting; I have never heard the word "decephalized" before --- in what literature in this used?

Decephalized humans would be great for the sex industry.

I've seen a lot here, but this takes the cake. I'm not sure if that post is a troll, assuming it is not:

Half of the energy and time of any decent person with morals goes into stopping smart psychopaths like that poster from doing whatever the heck they want.

I'm not religious, but it makes me wonder if the church is actually needed to keep those people in check.

If you want to be taken seriously you need to specify what morals is this violating exactly, it may be obvious to you but not to your readers.

As Shapiro says, you need to be taken seriously where it matters. If you sincerely need to ask which morals this violates, you show that you have no classical humanistic education. Such an education cannot be provided in a web forum.

It is sad that because of a couple of psychopaths tech people are not taken seriously outside of web forums.

Is easy to claim the moral high ground when you don't define it, meaning where are you drawing the line? If I lose a leg in an accident and some scientists (plus doctors) can make a clone of my leg and my leg only to reattach it on my body is that moral or amoral? If yes then what about the complete lower body? If yes what about everything below the neck?

I think you are being silly.

What's moral or amoral is dependant on whatever he is feeling at the moment. I very much doubt he has defined it.

> I'm not sure if that post is a troll

It's not. I've had this idea for some time, and I'm absolutely serious.

We already grow human cells in culture. It's like growing an extremely delicate plant. The HeLa cell line is derived from Henrietta Lacks, and she's been dead for some time. There's nothing wrong with growing and manipulating cells like this. Eukaryotic cells are as brainless as prokaryotic ones. This is how we do basic research.

We create multicellular tissue cultures, often using the extracellular matrix from cadavers. Again, basic research. Nothing wrong, nobody hurt.

If you can grow a human body without a head and brain, how is that ethically different from a plant? Please explain it to me. As long as you guarantee the brain never develops, it's ethically cleaner than telling a white lie.

Personhood requires a brain. Period.

I don't believe in a soul. So that's not an issue either.

Next explain to me why we shouldn't do this, because headless clones will cut organ transplant waiting lists to zero and help us cure cancer, diabetes, and every other human disease that doesn't directly involve the brain.

> Personhood requires a brain. Period.

Well, it requires a complex nervous system.

How many neurons are there outside of the brain?

How many neurons create a sensing, feeling being?

It's an assumption to say that the only way for consciousness around organic feeling to exist is through a brain. We don't know that.

I was under the impression that the nervous system outside the brain is only propagating signals back and forth, and all the actual compute is localized in the brain. If that's true, then the GP's idea makes sense; if it isn't, then that's a can of worms we need to sift through eventually.

"With thousands of brainless bodies kept alive on life support," It is questionable, if you can do this without a brain.

Have you seen Elysium? https://en.wikipedia.org/wiki/Elysium_(film)

I worked as a genetic engineer in human cell therapy: developmental biology doesn't really work that way. You can't just "decephalize" without causing massive secondary effects in body development and maturation - the nervous system is very much a central part and organizer of animal development, and also centrally important in a lot of the physiology you want to test when doing drug trials! And good luck keeping decephalized animals alive long enough to harvest outside a sterile lab. You don't need to be an edgelord billionaire to make a difference, but you'd benefit by learning more biology.

I don't have firsthand experience, but it seems like you could play with ectoderm development in conjunction with manual surgical techniques. Program the neural tube cells to die at a certain stage of development or when treated with certain media.

I think keeping the body alive will pose a much greater problem than preventing the brain from developing.

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?

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.

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.

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

Step by step, we are becoming obsolete...

Actually for drug research that's a good thing

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.

This isn't a chip for implanting inside the body; this is a microfluidic chip that replicates some body systems in the laboratory.

OK why the need for a physical chip, why not replicate in software?

Because we can't effectively model the behavior of human tissue in software.

by a long shot, too.

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.

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/

It's not a chip like a CPU. It's chemistry and biology.

These are being made as research tools, not as implants

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