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Why haven't biologists cured cancer?

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Re: Why haven't biologists cured cancer?

#41
post #35

Earlier quoted context omitted.

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 medicin…

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.

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Re: Why haven't biologists cured cancer?

#42
post #35

Earlier quoted context omitted.

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 medicin…

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.

Any technology purpose built to interface with cells would be a biological technology.

Re: Why haven't biologists cured cancer?

#44
post #36
post #30

Earlier quoted context omitted.

Yeah, I always make sure to say cancer(s) so we can skip the “it’s not one disease “ digression. It adds nothing to the conversation. According to Craig Venter, early detection is what we need to eliminate cancer(s): https://youtu.be/iUqgTYbkHP8?t=15m37s

early detection? there are not enough diagnostic tools that are already applied systematically right now for patients who have known cancers. this kind of idea is great on paper but hardly scales.

Enough diagnostic tools? Hah. Most cancer detection assays are pretty much garbage if you were to compare them to the latest advances in say deep learning image recognition models.

You can actually compare the sensitivity/specificity for PSA prostate screens versus something like ResNet for image recognition. The latter is in the high 90s for both metrics. The former can be as low as 0.06 for specificity if you want to actually achieve high sensitivity (detect prostate cancer with extremely extremely high false positives)

Re: Why haven't biologists cured cancer?

#45
post #25
post #21

This article is a good illustration of what's wrong with the current predominant approach in biology — it's all about genes and proteins, it's all way too reductionist to yield any meaningful higher-level outcomes. It's like trying to understand and manipulate an alien technology equivalent to a computer running a React web app, except you're only ever looking at and manipulating individual transistors in the CPU. As…

Its interesting how your example perfectly illustrates reductionism in action. There are so many things that can go wrong, which is why cancer is such a heterogeneous group of diseases. There are many mutations that can happen which can lead to cancer growth and they have nothing to do with electrophysiology.

That's the thing with Michael's research, he injected an oncogene into a tadpole, and then made the tumor cells reconnect with the surrounding tissue and become healthy again, all while the gene was still strongly expressed.

Re: Why haven't biologists cured cancer?

#46

Earlier quoted context omitted.

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.

Any technology purpose built to interface with cells would be a biological technology.

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.

Re: Why haven't biologists cured cancer?

#47
This reminds me of the company Loyal - a startup aiming at medical approaches to longevity by first treating pets/dogs. It's easier (I assume) from a regulation/moral standpoint to test therapies on animals instead of humans. I wonder if developing therapies for animal cancers first could be profitable, to bring in investment and prove a theory, and then expand to humans in a similar way.

Re: Why haven't biologists cured cancer?

#48
post #35

Earlier quoted context omitted.

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 medicin…

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.

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.

Re: Why haven't biologists cured cancer?

#49

The little anecdote about Peter Thiel about shitty physicists going into biology reminded me of a chapter from Richard Feynman's book, "Surely Your Joking Mr. Feynman". So it turns out Richard Feynman, after working in Los Alamos on the first nuclear bomb, and before going on to win a Nobel in Physics, actually did a stint as a biologist at CalTech. In fact he was doing some of the earliest work on ribosomes... so fu…

[flagged]

Did... did you just call Richard Feynman a "tool"?

Re: Why haven't biologists cured cancer?

#50

Earlier quoted context omitted.

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.

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 r…

What an incredible perspective on the world given your background. Thank you for taking the time to write all of that out.
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