5 ms·

Yep. (Doctor here) Im not sure who the target audience is for the article, but it strikes me as one where if the author were more knowledgeable on the subject,

Yep. (Doctor here) Im not sure who the target audience is for the article, but it strikes me as one where if the author were more knowledgeable on the subject, they would have many of the answers to what they are asking. It reads to me like someone writing "why are there still bugs in programming? Is it because of too many buttons on the screens?" Im in agreement with you that most people don't grasp just how medicine as an area of study is unfathomably complex. It mimics a fractal in the sense that the deeper we go in trying to understand things it just opens up a wider scope of investigation.

petermcneeley 2y ago
Most of the body is cells. Most of cancer would be rogue cells. Cancer can be cured if you can: 1. Identify rogue cells 2. Destroy the rogue cells. You can use technology to do both and pretty much ignore biology.
- deleted 2y ago
  [deleted]
- lanternfish 2y ago
  Any technology purpose built to interface with cells would be a biological technology.
  - petermcneeley 2y ago
    Many treatments today focus on simply killing the rogue cells. You dont really need to interface with something if your objective is to destroy it.
    - lolinder 2y ago
      Your first step is to identify it. What mechanism do you propose to use that doesn't somehow interface with biology?
- killjoywashere 2y ago
  Pathologist here (doctor who diagnoses cancer), who happens to have a degree in physics and works on diagnostic ML problems, including cancer. Cancer is not a simple anomaly detection problem. I mean, there's that, but so much more. These cells, each one of them, by their very nature, looks exactly like your normal healthy cells, on the outside. It's what's inside the cell that's going to kill you. The uncontrolled replication. There are 36 trillion cells in the human body. How are you going to monitor them all? Well, turns out we have several methods built in, collectively called the immune system. But again, they're mainly looking for "not self". Because if they were looking for "self" you'd have another problem, called auto-immunity. The uncertainty is real. It's not a hypothetical uncertainty. Combinatorics is a bitch. There are 3 billion base pairs per normal human cell. The difference between a normal cell and a cancer cell can be on a similar order (a cancer cell may have many billions or less than a billion base pairs). There are similar problems for the number of proteins, lipids, polysaccharides, metal ions etc, per cell. Three billion times 36 trillion, oh, and many generations of many of those 36 trillion over time. So, let's casually say a billion billion cells in a human life time. Times 3 billion base pairs. If one of those cells gets out of control, you've got a problem. Shockingly, only one in six people die of cancer. Only under the most austere circumstances can we partially characterize a single cancer cell, and even then we waste many, many other cancer cells to surface that one cell (e.g. single cell transcriptomics). Other methods allow us to examine many cells, but we can't examine them as closely (histology, histochemistry, immunochemistry, in situ hybridization, flow cytometry, targeted genomics, shotgun sequencing, karyotyping, etc), and we still never see most of the cells. To get a basic understanding, it's advisable to take the ground up approach used in statistical mechanics: in cancer, from the ground up, a single cell is the source of the initial problem. That cell and its progeny divide many times, let's say 30-40 times. Now you have a billion cells, maybe 10-100 billion cells. Every one of which is starting from an unmanaged state, highly vulnerable to additional mutations. And probably the cell of origin died 20 generations before you find the tumor. Even in a basic science research setting, it would be exceedingly challenging to demonstrate you had found "the cell of origin". This is very similar to physics: there are things we can know at one energy level that we can't know at another energy level. You can't explore Bose-Einstein condensates with the LHC. You're off by 20 orders of magnitude. You can't do single cell transcriptomics on a 1 kg en bloc cancer resection specimen, you're off by 20 orders of magnitude. Complicating matters, fission is actually pretty straight forward compared to biology. In fission, you've got a very small number of elements involved, at very high, specified purity. In biology, you can barely guess most of what the organism consumed in the last 24 hours, let alone what they've been exposed to over a lifetime. Cancer, nuclear physics, internet-scale computation, most of the really interesting problems: you can't just "take pictures" of the whole thing. It would be like assuming you can "just understand" what's happening in an actual nuclear explosion using some cameras and a sound understanding of math. Or the proposal that we could just understand the global economy by examining the ledger of all transactions. It's ridiculously beyond the realm of possible. Even in the Trinity explosion, a highly controlled, intensively studied nuclear explosion, we can't even be sure how many neutrons the beryllium-polonium initiator produced. 8? 10? Not really sure which atoms produced them, for sure. And how many got produced in each succeeding fission generation? Meh? I mean, we can do some statistics, but that's it. That's roughly the scale of the problem we're dealing with in cancer research: where'd the thing come from? And where's it going? Statistically, we can make some guesses, but no one understands the whole thing.
- Zenzero 2y ago
  I'll admit this gave me a really good laugh.
  - petermcneeley 2y ago
    But will you have the last laugh?
- raincole 2y ago
  https://xkcd.com/793/ https://xkcd.com/793/
  - petermcneeley 2y ago
    I feel like this one applies better https://xkcd.com/1831/ https://xkcd.com/1831/
- yjftsjthsd-h 2y ago
  > Cancer can be cured if you can: > 1. Identify rogue cells 2. Destroy the rogue cells. Oh, is that all?:D And which of those do we have the tech to do?
  - stef25 2y ago
    3. Don't destroy good cells
    - pvaldes 2y ago
      Even better, as we are writing a wish list: 4. Reinforce control of the chemical polluters Push to assure that as much people as possible are supplied with food and water that are clean of cancer triggering chemicals. Educate people about sunburns is useful also, but people will rarely get leukemia or pancreatic cancer by sun exposure alone. The sad truth is that most people will not be grateful for --not having-- cancer or --not going-- into a fat accumulation spiral by chemicals breaking the body fat system. People just take this for granted, or expect somebody volunteering to do this work for free. Is not a lack of will, is a lack of resources. Banners are still one of the most powerful tools against cancer and the most underrated one.
- magicalhippo 2y ago
  How to draw an owl: 1. Draw some circles. 2. Draw the rest of the owl.
- slowmovintarget 2y ago
  The human body is a non-orthogonal system. Everything in it is interconnected and exists in interrelated dynamic tension. We're still finding new structures in living humans that went undetected in cadaver analysis [1]. If you've written any code at all, you know that a non-orthogonal system is incredibly complex. It isn't just a matter of complexity scaling linearly with the count of the individual parts. Complexity scales with the interactions between each component, and between the assemblages of those components that have emergent interactions. Change one line of code, and you get wildly different behavior in another part of the system, or seemingly nothing for a long time until the system deletes its own database suddenly one day. Curing cancer is a dramatically broad statement, because each kind is different, interacts with a different part of the body, and has different ways of growing and sustaining itself. Each intervention causes a cluster of unintended side-effects, again, because the body is a non-orthogonal system. Even your simple statements fall flat. Most cancer cells disguise themselves as normal cells from the perspective of the body's immune system. It's why the cancer can grow at all. The other factor is that most things that would kill cancer cells would kill cells... in general. Pull one thread wrong, fix one bug the wrong way... you end up doing more harm than good. Maybe we'll get to a point where we have combinations of nanotech and gene therapies that eliminate most cancers. But it won't be simple. Getting there in an ethical fashion makes it even harder. How do we experiment with this kind of nanotech (which is not even off the ground yet). How do we experiment with this kind of gene therapy (we have more traditional paths to tread here, but there are still some quandaries). We're just not there yet, and I doubt it will ever be something as reductive as your two items. [1] https://www.science.org/content/article/scientists-say-they-ve-found-new-human-organ https://www.science.org/content/article/scientists-say-they-... (2018)
  - Zenzero 2y ago
    > The other factor is that most things that would kill cancer cells would kill cells... in general. Pull one thread wrong, fix one bug the wrong way... you end up doing more harm than good. Yep. It's like modifying an undocumented API where there are tens of thousands of endpoints and you know there are a few dozen services that rely on each endpoint, and probably a few dozen more that nobody knows about. You are only allowed test runs that are expected to succeed, since test failures = death. Your dev environment is a mouse. Every change gets pushed to prod with no option to revert.

petermcneeley 2y ago

Most of the body is cells. Most of cancer would be rogue cells. Cancer can be cured if you can: 1. Identify rogue cells 2. Destroy the rogue cells. You can use technology to do both and pretty much ignore biology.

deleted 2y ago
[deleted]
lanternfish 2y ago
Any technology purpose built to interface with cells would be a biological technology.
- petermcneeley 2y ago
  Many treatments today focus on simply killing the rogue cells. You dont really need to interface with something if your objective is to destroy it.
  - lolinder 2y ago
    Your first step is to identify it. What mechanism do you propose to use that doesn't somehow interface with biology?
killjoywashere 2y ago
Pathologist here (doctor who diagnoses cancer), who happens to have a degree in physics and works on diagnostic ML problems, including cancer. Cancer is not a simple anomaly detection problem. I mean, there's that, but so much more. These cells, each one of them, by their very nature, looks exactly like your normal healthy cells, on the outside. It's what's inside the cell that's going to kill you. The uncontrolled replication. There are 36 trillion cells in the human body. How are you going to monitor them all? Well, turns out we have several methods built in, collectively called the immune system. But again, they're mainly looking for "not self". Because if they were looking for "self" you'd have another problem, called auto-immunity. The uncertainty is real. It's not a hypothetical uncertainty. Combinatorics is a bitch. There are 3 billion base pairs per normal human cell. The difference between a normal cell and a cancer cell can be on a similar order (a cancer cell may have many billions or less than a billion base pairs). There are similar problems for the number of proteins, lipids, polysaccharides, metal ions etc, per cell. Three billion times 36 trillion, oh, and many generations of many of those 36 trillion over time. So, let's casually say a billion billion cells in a human life time. Times 3 billion base pairs. If one of those cells gets out of control, you've got a problem. Shockingly, only one in six people die of cancer. Only under the most austere circumstances can we partially characterize a single cancer cell, and even then we waste many, many other cancer cells to surface that one cell (e.g. single cell transcriptomics). Other methods allow us to examine many cells, but we can't examine them as closely (histology, histochemistry, immunochemistry, in situ hybridization, flow cytometry, targeted genomics, shotgun sequencing, karyotyping, etc), and we still never see most of the cells. To get a basic understanding, it's advisable to take the ground up approach used in statistical mechanics: in cancer, from the ground up, a single cell is the source of the initial problem. That cell and its progeny divide many times, let's say 30-40 times. Now you have a billion cells, maybe 10-100 billion cells. Every one of which is starting from an unmanaged state, highly vulnerable to additional mutations. And probably the cell of origin died 20 generations before you find the tumor. Even in a basic science research setting, it would be exceedingly challenging to demonstrate you had found "the cell of origin". This is very similar to physics: there are things we can know at one energy level that we can't know at another energy level. You can't explore Bose-Einstein condensates with the LHC. You're off by 20 orders of magnitude. You can't do single cell transcriptomics on a 1 kg en bloc cancer resection specimen, you're off by 20 orders of magnitude. Complicating matters, fission is actually pretty straight forward compared to biology. In fission, you've got a very small number of elements involved, at very high, specified purity. In biology, you can barely guess most of what the organism consumed in the last 24 hours, let alone what they've been exposed to over a lifetime. Cancer, nuclear physics, internet-scale computation, most of the really interesting problems: you can't just "take pictures" of the whole thing. It would be like assuming you can "just understand" what's happening in an actual nuclear explosion using some cameras and a sound understanding of math. Or the proposal that we could just understand the global economy by examining the ledger of all transactions. It's ridiculously beyond the realm of possible. Even in the Trinity explosion, a highly controlled, intensively studied nuclear explosion, we can't even be sure how many neutrons the beryllium-polonium initiator produced. 8? 10? Not really sure which atoms produced them, for sure. And how many got produced in each succeeding fission generation? Meh? I mean, we can do some statistics, but that's it. That's roughly the scale of the problem we're dealing with in cancer research: where'd the thing come from? And where's it going? Statistically, we can make some guesses, but no one understands the whole thing.
Zenzero 2y ago
I'll admit this gave me a really good laugh.
- petermcneeley 2y ago
  But will you have the last laugh?
raincole 2y ago
https://xkcd.com/793/ https://xkcd.com/793/
- petermcneeley 2y ago
  I feel like this one applies better https://xkcd.com/1831/ https://xkcd.com/1831/
yjftsjthsd-h 2y ago
> Cancer can be cured if you can: > 1. Identify rogue cells 2. Destroy the rogue cells. Oh, is that all?:D And which of those do we have the tech to do?
- stef25 2y ago
  3. Don't destroy good cells
  - pvaldes 2y ago
    Even better, as we are writing a wish list: 4. Reinforce control of the chemical polluters Push to assure that as much people as possible are supplied with food and water that are clean of cancer triggering chemicals. Educate people about sunburns is useful also, but people will rarely get leukemia or pancreatic cancer by sun exposure alone. The sad truth is that most people will not be grateful for --not having-- cancer or --not going-- into a fat accumulation spiral by chemicals breaking the body fat system. People just take this for granted, or expect somebody volunteering to do this work for free. Is not a lack of will, is a lack of resources. Banners are still one of the most powerful tools against cancer and the most underrated one.
magicalhippo 2y ago
How to draw an owl: 1. Draw some circles. 2. Draw the rest of the owl.
slowmovintarget 2y ago
The human body is a non-orthogonal system. Everything in it is interconnected and exists in interrelated dynamic tension. We're still finding new structures in living humans that went undetected in cadaver analysis [1]. If you've written any code at all, you know that a non-orthogonal system is incredibly complex. It isn't just a matter of complexity scaling linearly with the count of the individual parts. Complexity scales with the interactions between each component, and between the assemblages of those components that have emergent interactions. Change one line of code, and you get wildly different behavior in another part of the system, or seemingly nothing for a long time until the system deletes its own database suddenly one day. Curing cancer is a dramatically broad statement, because each kind is different, interacts with a different part of the body, and has different ways of growing and sustaining itself. Each intervention causes a cluster of unintended side-effects, again, because the body is a non-orthogonal system. Even your simple statements fall flat. Most cancer cells disguise themselves as normal cells from the perspective of the body's immune system. It's why the cancer can grow at all. The other factor is that most things that would kill cancer cells would kill cells... in general. Pull one thread wrong, fix one bug the wrong way... you end up doing more harm than good. Maybe we'll get to a point where we have combinations of nanotech and gene therapies that eliminate most cancers. But it won't be simple. Getting there in an ethical fashion makes it even harder. How do we experiment with this kind of nanotech (which is not even off the ground yet). How do we experiment with this kind of gene therapy (we have more traditional paths to tread here, but there are still some quandaries). We're just not there yet, and I doubt it will ever be something as reductive as your two items. [1] https://www.science.org/content/article/scientists-say-they-ve-found-new-human-organ https://www.science.org/content/article/scientists-say-they-... (2018)
- Zenzero 2y ago
  > The other factor is that most things that would kill cancer cells would kill cells... in general. Pull one thread wrong, fix one bug the wrong way... you end up doing more harm than good. Yep. It's like modifying an undocumented API where there are tens of thousands of endpoints and you know there are a few dozen services that rely on each endpoint, and probably a few dozen more that nobody knows about. You are only allowed test runs that are expected to succeed, since test failures = death. Your dev environment is a mouse. Every change gets pushed to prod with no option to revert.