The end of Infectious Disease

Tripamang

Tripamang

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I did a rather shit job of explaining why I thought cures were easy in the politics thread, here is my second shot at it. Vaccine's have dated back as far as the 10th century China and first recorded in western medicine in the mid-to late 1700's. We've known that unique markers (antibodies) are how the body identifies diseases that it's already encountered and uses it to trigger a defense since the mid 80's. So if you can train your body to identify these markers you can make yourself immune to those diseases, which is the way a vaccine works. It's limited to diseases that haven't embedded their DNA into our own cells to hide themselves, but pretty much everything else including cancer can be identified this way (Possibly even plaque diseases like Alzheimers and Parkinsons).

What makes me crazy about this is that there has been no coordinated effort to identify these markers. We know how the immune system works, we know the value of these markers but there has been no effort to identify them all. Let that sink in, we've skipped out on identifying antibodies when we knew they could eventually cure most human infectious disease as well as cancer because we had nothing that could immediately use them. This is not to say that people weren't finding them or researching them, there was just no special set of money set aside or some organization trying to get people together to find them. Now we have devices like this: Engineers design programmable RNA vaccines which is more or less a vaccine printing machine. If you know the antibody, you can print off the vaccine to match it. No longer do you have to create a weakened version of the disease to breed to create a vaccine.. just print and cure.

I can't say how much further we could of been ahead right now if there had been a coordinated effort in identifying the antibodies, or a large research project to make an RNA printer like the MIT group but you can't help but wonder. With advances in CRISPR we'll get the point where we can even purge things like AIDS and Herpes that have embedded themselves inside our cells. The end of infectious disease is within reach.

From my perspective though this inability to get our shit together is just a byproduct of a broken research system and a market that provides little rewards for private industry to cure disease. Private industry could of done the work to identify them and brought together some of the brightest people in the world to do it, public institutions could of done the same.
 
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Kithani

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That thread was all about how we can't cure anything. This thread is about how we can cure everything, I think.
 
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iannis

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Some things you just can't cure. A lot of things you can. Some things you just can't.


You need to consider that there is a limit to the physical space available in the blood. There is an actual physical limit. You need to consider that what we have named the immune system is not a conscious entity, it is a set of distinct, specalized processes that occur within the blood and within individual unhealthy cells. Those processes are for the most part not pro-active, they are re-active. The immune system does not monitor health, it reacts to the absence of health -- as defined in very specific chemical ways.

Viral agents are particularly troublesome. You can innoculate, but you cannot truly prevent a viral infection. Not with our current technology, and probably not ever. Viruses are small protein strands. They're weeds in your yard, basically. The cell is in most ways a protein factory. Cells create, absorb, shed, and exchange proteins. That is an integral part of normal function. All of these strands have specific shapes based on exactly what they're made of and in exactly what order. There are an awful lot of shapes that can be made, but as a practical matter they are finite. If you wanted to prevent a virus from infecting the medium before it even encountered a cell you would have to identify it's specific shape and you would have to create a complementary shape to neutralize it. That's just how you would have to do it. And there is a reason that the body has never evolved a strong mechanism to do exactly that -- there are overlaps in shapes and this is not a directed process. This is a chemical process. It's dumb fucking luck, literally it's dumb fucking luck, if you hit the target or if you hit something that just kinda looks like the target if you squint. That's what a lot of autoimmune diseases are.

It's not that we're too dumb to know what the shapes are, or that we're too greedy to produce chemical compounds which could turn viruses to salt in your bloodstream. It's more that it's, when you look at how the immune system works and what's going on i the body... it's just a spectacularly bad idea.

So that's not what vaccines do. Innoculation prepares the immune response to be more efficient. That's often effective, and it's a damn good thing, but it is not a cure even using the most abstract definition. An innoculation does not give you immunity in the way that you seem to be thinking of it. You will still be infected by whichever virus it is, should you encounter it in the environment. The immune system doesn't bother with the virus. It's not proactive. That's what your skin is for, and why epithelial tissue is so short lived. The immune system responds to signals from the infected cells themselves... signals that come in the form of little protein strands. Which you may or may not interfere with trying to inject some voodoo into the system. There's a reason that testing takes decades, and that computational power has advanced the field so significantly.

When you talk about curing viruses, you're talking about the population rather than the individual. That we can do. But it literally takes 2 generations. And don't go opening up any smallpox graves. Because in this context cure doesn't mean immunity. And viruses don't die. They decay.

That's totally different than bacterial infections. You can be much more direct with bacterial infections, and we are. Fungal infections... completely different again. Parasitic infections... completely different.

It is also completely different again from both bacterial, fungal, parasitic infections and things like Alzheimers or Parkinsons. These are all very different things. Don't let the success that we've had with the most obvious and easiest of the three fool you into thinking it is even possible to have the same success with everything else.

Even with magical nanotechnology, there's still going to be a physical limit to the space available in the blood. There's still going to be proscripted interactions. I mean star trek medicine is cool, but that's just not reality.

It's not gloom and doom, not at all. We're living in a medical golden age. But it's science, it's not magic. These are doctors and researchers, they aren't Gods.
 
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ZyyzYzzy

ZyyzYzzy

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Tripamang said:
I did a rather shit job of explaining why I thought cures were easy in the politics thread, here is my second shot at it. Vaccine's have dated back as far as the 10th century China and first recorded in western medicine in the mid-to late 1700's. We've known that unique markers (antibodies) are how the body identifies diseases that it's already encountered and uses it to trigger a defense since the mid 80's. So if you can train your body to identify these markers you can make yourself immune to those diseases, which is the way a vaccine works. It's limited to diseases that haven't embedded their DNA into our own cells to hide themselves, but pretty much everything else including cancer can be identified this way (Possibly even plaque diseases like Alzheimers and Parkinsons).

What makes me crazy about this is that there has been no coordinated effort to identify these markers. We know how the immune system works, we know the value of these markers but there has been no effort to identify them all. Let that sink in, we've skipped out on identifying antibodies when we knew they could eventually cure most human infectious disease as well as cancer because we had nothing that could immediately use them. This is not to say that people weren't finding them or researching them, there was just no special set of money set aside or some organization trying to get people together to find them. Now we have devices like this: Engineers design programmable RNA vaccines which is more or less a vaccine printing machine. If you know the antibody, you can print off the vaccine to match it. No longer do you have to create a weakened version of the disease to breed to create a vaccine.. just print and cure.

I can't say how much further we could of been ahead right now if there had been a coordinated effort in identifying the antibodies, or a large research project to make an RNA printer like the MIT group but you can't help but wonder. With advances in CRISPR we'll get the point where we can even purge things like AIDS and Herpes that have embedded themselves inside our cells. The end of infectious disease is within reach.

From my perspective though this inability to get our shit together is just a byproduct of a broken research system and a market that provides little rewards for private industry to cure disease. Private industry could of done the work to identify them and brought together some of the brightest people in the world to do it, public institutions could of done the same.
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Guyz, antibodies are so ez to make. Plus there is alwayz cheap easy animal models for early research.

Do you have any idea how difficult it can be to make good, monoclonal antibodies for some proteins?
 
Tripamang

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ZyyzYzzy said:
Guyz, antibodies are so ez to make. Plus there is alwayz cheap easy animal models for early research.

Do you have any idea how difficult it can be to make good, monoclonal antibodies for some proteins?
Click to expand...

That's a really stupid response, we develop tools to make tasks easier so we can accomplish more. Why would antibodies be any fucking different? If we followed your logic we'd have no progress at all because it was "difficult".

iannis iannis thanks for the response, yea I could of worded it better. It won't necessarily cure any infectious disease but it can slow/eradicate them if it's done properly eventually eliminating them. You can also use them to train T cells for the body to find cancer (immunothearpy). They've had success with RNA vaccines and Alzheimer's as well. http://medicalxpress.com/news/2016-07-world-alzheimer-vaccine.html

This is also pretty cool, they've modified mosquitoes so that they die very quickly after breeding. They're trying to wipe out the species that carry Zika, dengue, yellow fever and chikungunya. There are other groups that are working on different modifications that will prevent them from transmitting diseases like malaria using a gene drive force the change through the population and in the process eliminate the disease.

http://phys.org/news/2016-10-brazil-mutant-mosquitoes-diseases.html
 
ZyyzYzzy

ZyyzYzzy

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Tripamang said:
That's a really stupid response, we develop tools to make tasks easier so we can accomplish more. Why would antibodies be any fucking different? If we followed your logic we'd have no progress at all because it was "difficult".

iannis iannis thanks for the response, yea I could of worded it better. It won't necessarily cure any infectious disease but it can slow/eradicate them if it's done properly eventually eliminating them. You can also use them to train T cells for the body to find cancer (immunothearpy). They've had success with RNA vaccines and Alzheimer's as well. http://medicalxpress.com/news/2016-07-world-alzheimer-vaccine.html

This is also pretty cool, they've modified mosquitoes so that they die very quickly after breeding. They're trying to wipe out the species that carry Zika, dengue, yellow fever and chikungunya. There are other groups that are working on different modifications that will prevent them from transmitting diseases like malaria using a gene drive force the change through the population and in the process eliminate the disease.

http://phys.org/news/2016-10-brazil-mutant-mosquitoes-diseases.html
Click to expand...

You are comlletely trivializing actual hard things to accomplish in the lab. No shit groups are coming up with ways to produce better antibodies and antibodies against proteins/targets that don't normally elicit immune responses ?
 
Tripamang

Tripamang

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ZyyzYzzy said:
You are comlletely trivializing actual hard things to accomplish in the lab. No shit groups are coming up with ways to produce better antibodies and antibodies against proteins/targets that don't normally elicit immune responses ?
Click to expand...

Then what the fuck was your point? Some of them are going to be hard and take longer, others are easy targets. You can pick the ones you choose to research and prioritize based on the technology at hand and what will have the biggest impact. If this was organized the progress would be faster in identifying them, and if the proper funding was put behind it the tool creation they would also advance quicker. It takes a lot of money to develop the tools like the RNA vaccine printer and there aren't a lot of intuitions that afford to pay for this kind of development.

These are hard problems, but if we organize and fund them properly the progress can happen much quicker. This isn't like the early 20th century when we had no clue what these diseases were or how we could even approach solutions. We're at the end where we've identified weaknesses and it's developing the tools to exploit them, it's a much smaller hurdle to over come. That's not trivializing the work, it's recognizing where we are in our understanding of disease and how few steps there are left until we have the tools to stop/control them.
 
ZyyzYzzy

ZyyzYzzy

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Tripamang said:
Then what the fuck was your point? Some of them are going to be hard and take longer, others are easy targets. You can pick the ones you choose to research and prioritize based on the technology at hand and what will have the biggest impact. If this was organized the progress would be faster in identifying them, and if the proper funding was put behind it the tool creation they would also advance quicker. It takes a lot of money to develop the tools like the RNA vaccine printer and there aren't a lot of intuitions that afford to pay for this kind of development.

These are hard problems, but if we organize and fund them properly the progress can happen much quicker. This isn't like the early 20th century when we had no clue what these diseases were or how we could even approach solutions. We're at the end where we've identified weaknesses and it's developing the tools to exploit them, it's a much smaller hurdle to over come. That's not trivializing the work, it's recognizing where we are in our understanding of disease and how few steps there are left until we have the tools to stop/control them.
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Okay please stop. You have zero researcj experience. Please tell me how making a cure is easy? As to the antibodies, in basic research where you are just trying to first identify possible targets to invesitgate, guess what you can't easily prioritize based on ease of antibody development.

You are the retard who said cures are easy to find, eat your fucking words and shut up.
 
Tuco

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iannis said:
Even with magical nanotechnology, there's still going to be a physical limit to the space available in the blood. There's still going to be proscripted interactions. I mean star trek medicine is cool, but that's just not reality.
Click to expand...
With magical nanotech, won't we be able to easily identify virus elements and separate them from other stuff in ways we can't now? Such that we aren't squinting with cumbersome tools, but are identifying very small structures with precision far beyond what we have now?
 
Tripamang

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ZyyzYzzy said:
Okay please stop. You have zero researcj experience. Please tell me how making a cure is easy? As to the antibodies, in basic research where you are just trying to first identify possible targets to invesitgate, guess what you can't easily prioritize based on ease of antibody development.

You are the retard who said cures are easy to find, eat your fucking words and shut up.
Click to expand...

You're again confusing a lack of good tools and coordinated research with me saying these are simple problems. I don't know how else to explain this to you, it just seems like you some sort of mental block. Yes these are hard problems, yes it's difficult to identify them but that difficulty is caused by us not having the right tools to do it efficiently. Whether the solution is computer simulations of the disease or it's a piece of machinery to automate the testing, these are both things we can prioritize and build to make the progress faster and easier. By picking easy things to research I was referring to diseases where we've identified these targets and prioritizing their development into vaccines and choosing other diseases that have a large impact to society and throwing money at discovering their markers.

You're talking like these are insurmountable problems, they aren't.
 
ZyyzYzzy

ZyyzYzzy

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Tripamang said:
You're again confusing a lack of good tools and coordinated research with me saying these are simple problems. I don't know how else to explain this to you, it just seems like you some sort of mental block. Yes these are hard problems, yes it's difficult to identify them but that difficulty is caused by us not having the right tools to do it efficiently. Whether the solution is computer simulations of the disease or it's a piece of machinery to automate the testing, these are both things we can prioritize and build to make the progress faster and easier. By picking easy things to research I was referring to diseases where we've identified these targets and prioritizing their development into vaccines and choosing other diseases that have a large impact to society and throwing money at discovering their markers.

You're talking like these are insurmountable problems, they aren't.
Click to expand...
I am not. Please tell me about the technique and procedure, or instrumention you would come up with to employ ubiquitously for protein identification, quantification, imaging, or anything? That is just as great or even a greater challenege.

And do you not think there is work into this? Hell one go around that was developed to produce antibodies for non-immunogenic proteins is to expose a mouse (rabbit, whatever you are using) to the protein and then inducing an artificial immune response by injecting various chemicals (interleukins, etc...) to force an immune response.

Again, all this makes it inherently difficult. Idk why you think if people just used RNA printers everything would magically be cured. Guess what "printing"has veen around for a while. You can print DNA, RNA and amino acid oligos pretty easily abd cheaply (well order them).
 
ZyyzYzzy

ZyyzYzzy

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Tuco said:
With magical nanotech, won't we be able to easily identify virus elements and separate them from other stuff in ways we can't now? Such that we aren't squinting with cumbersome tools, but are identifying very small structures with precision far beyond what we have now?
Click to expand...
We can do this now with proteins that bind to sites of interest of biomolecules, mass spectroscopy and x-ray crystallography (and more). These are just very difficult .
 
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Mario Speedwagon

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If infectious disease is so easy to eradicate then why are there still black people?


Checkmate atheists.
 
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P

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Tripamang said:
That's a really stupid response, we develop tools to make tasks easier so we can accomplish more. Why would antibodies be any fucking different? If we followed your logic we'd have no progress at all because it was "difficult".

iannis iannis thanks for the response, yea I could of worded it better. It won't necessarily cure any infectious disease but it can slow/eradicate them if it's done properly eventually eliminating them. You can also use them to train T cells for the body to find cancer (immunothearpy). They've had success with RNA vaccines and Alzheimer's as well. http://medicalxpress.com/news/2016-07-world-alzheimer-vaccine.html
Click to expand...

My wife worked in the lab that developed the therapies in your link, and I am a scientist developing immunotherapies, so I know a bit about these topics. Long story short: At my company, and in many labs around the world, money is not an issue. However, the entire R&D process is filled with scientific bottlenecks that simply require a lot of time before

Identifying immunogenic proteins is one bottleneck (though less so than it was "back in the day"), and even when are sitting on a sequence for a known immunogenic protein you'd be surprised at how much time and money it takes to identify the proper epitopes. New higher throughput in vitro screening methods are handy for narrowing down peptide pools but they also are prone to false positives and negatives and always require follow-up in vivo studies in large animals. On top of that you need to verify the specificity of the immune response you are elicited. Look no further than the recent deaths in some of the CAR-T trials where you are loading up a patient with activated T cells and even tiny levels of off-target protein expression in tissues such as the heart and lungs can create a cytokine storm and kill a patient. Or refer to the recent patient deaths in the Juno trials where the chemotherapy standard of care treatment compounded the toxicity of their T cells and killed some patients before the trial was halted and modified. These are not trivial issues and the reason you don't see these headlines more often is because every single therapy requires years of research and extensive cellular and animal studies.

And now you get into the cost and time for multiple studies in large animals, and for many emerging infectious diseases we are severely hindered by the lack of a standard animal model and/or any correlate for protection. Take EBOLA for example. My company, and many others, are producing pretty impressive titers in humans and everyone is asking: why isn't a there a licensed vaccine out there yet? But how do we know what titers are sufficient for protection? How do we even compare two different companies' humoral response data when they are both using their in-house ELISA protocols because the outbreak is too fresh for a historical standard to be developed? How do we know that protection isn't T cell-mediated? If it is, then we need to develop an ELISpot assay, and validate it, and standardize it. And then for all of this we need an animal model in order to even start looking at efficacy, but the animal models take time to develop because if the disease progression in animals doesn't mimic the human condition then we are just wasting time anyways. And then for EBOLA, what mode of infection should we use? Some vaccines have different effectiveness if you challenge the animals with inhalation of virus compared to IM or SC administration?

Same story for Zika: emerging disease, requires a new set of assays, animal models, and challenge study designs, all of which need to be validated, and then need to be standardized, and then need to be adopted. Big, big companies are pouring money and man hours into answering these questions.

Tripamang said:
What makes me crazy about this is that there has been no coordinated effort to identify these markers. We know how the immune system works, we know the value of these markers but there has been no effort to identify them all. Let that sink in, we've skipped out on identifying antibodies when we knew they could eventually cure most human infectious disease as well as cancer because we had nothing that could immediately use them.
Click to expand...

I think the main problem you fail to address is that identifying antigens and developing antibodies is only a small piece of the puzzle, and we can never know if something "works" until we put it through a randomzied controlled clinical trial. It's just not feasible to crank out studies like these because the cost is prohibitive and the consequences for failure can be catastrophic (but now we are getting into completely separate topics).

The second problem I have with this quote is you state that "we know how the immune system works." That's a pretty bold claim, and as much as I wish you were right, it's just not true. The majority of the immune system is still a black box to us, and we have just enough knowledge to know which levers to pull to get a general result, which makes the vaccines and therapies that are available today pretty miraculous if you think about it.

I do agree with you that it would be great to have a bit more standardization. A lot of competitors are working in parallel to develop these assays, so there's probably some considerable overlap in their efforts. However, this also serve to accelerate research, since there is incentive to "win the race" to market. TCentralizing and standardizing everything can also stifle creativity, since you need decisions being made at the top about where to spend the money and time. There's not an easy answer, unfortunately.
 
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ZyyzYzzy

ZyyzYzzy

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Hell, the botulinum toxin standard most people would consider archaic. Lethal mouse model, and that is a hugely profitable protein witha ton of work still being done. And yet that is the "standard" that is relied on.
 
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