
The fight against cancer: The promise of HIF-1 inhibitors - rustoo
https://www.editage.com/insights/the-fight-against-cancer-the-promise-of-hif-1-inhibitors
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choeger
Whenever I read something like this I dread how much we are still lacking in
medical research. An observation like this should, in an ideal world, be
subject to intense simulations in sophisticated models. The results should
then immediately apply to a large percentage of patients. Consequently, an
individual treatment option should be on the table in weeks and its
application should result in an immediate refinement of said models.

As of today, this whole iterative cycle takes years, if it is ever closed at
all.

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GlenTheMachine
I assume you mean computer models?

The problem here is that, although it might be possible to figure out a drug's
efficacy by modeling just it's primary mode of action, in order to find it's
side effects you have to model every other interaction it might have.

In other words - we can tell whether a drug will kill cancer cells just by
looking at how it interacts with cancer cells. But to figure out how it
interacts with the rest of the body, you have to be able to model the entire
body with nearly perfect fidelity. And this is not just a problem of having
insufficient knowledge - although it is that - we just don't understand all of
body's systems anywhere near well enough to write such a model) but it's also
a compduting power - recall that the protein folding problem is NP-Hard with
an enormous number of degrees of freedom. In some cases it can have several
hundred degrees of freedom, and the number of cases you have to check scales
as the factorial of that.

Maybe someday we'll have numerical techniques that can solve the protein
folding problem and other organic chemistry problems using achievable
computing power. But we can't today. Even if we had a perfect atom-for-atom
model of the human body we couldn't run it.

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ethbro
Or, to put it another way, why would drug companies be spending billions of
dollars on animal model trials if they could simulate drugs in silicon?

A teaspoon of humility when talking about why another discipline doesn't 'Just
do X?' is well served.

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choeger
You might have misread my comment. I find it sad that we do not have these
models. I am well aware that right now it is not possible. I do blame on
pharma however for not putting massive amounts of money into this fundamental
research. I did a lot of modeling and simulation and I know that chemistry and
molecular biology simulation tools exist. But I never encountered a call for
academic contributions to increase performance or supply general numerical or
computational techniques. from my pov the civil engineering simulators (using
odes,dates, and pdes) where completely separate from the chemistry world
(often using odes and daes).

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GlenTheMachine
I can tell you that there is a not inconsiderable amount of effort going into
the computational protein folding problem. I do not know where this funding
comes from though. It's just a fundamentally hard problem, and it isn't clear
(to me, at least) that it can really be solved. Quantum computing, maybe, but
I'm not knowledgeable in that. Short of that, though, it might always turn out
to be computationally more efficient to just "build" an analog body. There's
no guarantee that we can simulate every physical process at faster than
realtime speeds with CPUs.

I don't think you're going to find a single line of accounting that says
"improve biochemical knowledge of the body for modeling purposes".
Essentially, all fundamental research in medicine falls into this bucket.

