
The Quant King, the Drug Hunter, and the Quest to Unlock New Cures - daschaefer
https://www.bloomberg.com/news/features/2018-06-12/a-quant-king-and-a-drug-hunter-join-in-a-quest-to-find-new-cures
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arandr0x
For this stage of drug discovery (finding potential hits off of ligand
databases, finding potential targets, and refining ligands in silico without
running real high-throughput lab work) machine learning may work better at
lesser cost. It's the direction (some) research is going right now.

Of course the real cost of drug development is running clinical trials, and
losing something like 90% of ligands because they don't make it into the
bloodstream, can't be synthesized at scale, or wind up having no efficacy in
vivo for no reason anyone can fathom.

(Even making "copycat drugs" where you pick a known target, known ligand
class, and try to minimally alter the synthesis process to get a newly-
patentable product can sometimes have odd surprises, including the kind of odd
surprise where being more specific to the identified target leads to
diminished efficacy.)

This goes to show that fundamental research in biochemistry is still needed
and we are nowhere near having "cracked the code", genomics notwithstanding.

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ShabbosGoy
> This goes to show that fundamental research in biochemistry is still needed
> and we are nowhere near having "cracked the code", genomics notwithstanding.

Personalized medicine is the future. You will find medication that is tweaked
slightly at the molecular level to optimize therapeutic effects for the
_individual_ as opposed to a population of individuals.

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tomcam
How does that happen without $1 billion worth of test requirements from the
FDA?

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arandr0x
There are drug classes where for many reasons, some IP related, there are
multiple (all FDA approved) very similar molecules, or the same molecule in
different formulations. Those drugs all have some measure of efficacy
(otherwise they wouldn't be approved) but there's always somebody in the trial
on whom the drug didn't work at all (or somebody who died). Ideally
personalized medicine would tell you whether you're that somebody, and you'd
pick a different drug.

For most drug classes though the cost of obtaining enough patient information
to make the call in the first place, even if it was feasible, is pretty high
relative to just giving you a "test" with a given drug. The argument is often
made for cancer because the drugs are more expensive and they tend to be given
as cocktails (which means, more costs, more side effects). But with the way
medicine currently is, it feels like even if hypothetically you could tell
from a blood draw and a tumor biopsy that drug 1 is going to be 99% as
effective as 4 first-line drugs together, patients for whom that 1% chance
means they might die are probably going to go for the cocktail.

It's possible personalized medicine will lead to cheaper trials, and then
cheaper approvals. For example instead of saying "I will make a drug that
cures (alcoholism/cancer/MS/Alzheimer's) and it has to not kill patients and
also happen to cure (alcoholism/cancer/MS/Alzheimer's) in a relatively large
subset of the population, that I will spend tens of millions of dollars
finding, testing, adjusting, retrying, etc" you could say "I will make a drug
that cures dementia in female Caucasian patients between the age of 60 and 70
that have Southern European ancestry, eat a low-carb diet, and have a couple
specific DNA markers. I will recruit a smaller sample of this population, get
results, and my (much cheaper) drug can get approved for this population.
Other, also cheap drugs will follow for (men/Asians/people over 80)." Now you
have a feature engineering problem where you get to spend hundreds of millions
of dollars paying data scientists to figure out that South European ancestry
and some random protein that moves methyl groups around are the categories to
structure your trial around. There's no free lunch.

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vapemaster
Yup. And judging by their team and strategy they are likely using a highly
empirical ligand discovery platform (ie DEL) and using the (admittedly best in
class) MD for guiding med chem. Taking the hard problem of drug discovery and
then saying you are going to do rational design (a road riddled with dead
bodies) on dynamic alloseteric sites of challenging targets is a lofty goal to
put it mildly..

~~~
stochastic_monk
Dead bodies as in patients harmed or failed attempts?

~~~
carbocation
Failed attempts. The regulatory framework in the US and Europe is still pretty
good at protecting patients.

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Tehchops
I see you there, Ubuntu desktop :)

Interesting he's using a mbp box as a monitor stand.

On to a more serious note: is this kind of computing work sped up with GPUs?

~~~
vapemaster
Custom ASIC hardware for running molecular dynamics. check out Anton [1]

[1]
[https://en.m.wikipedia.org/wiki/Anton_(computer)](https://en.m.wikipedia.org/wiki/Anton_\(computer\))

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kolbe
I don't understand companies like this. Its founder is worth something like
$5b, but instead of financing this venture with a tiny fraction of his net
worth, Shaw decided to go get funding from several other firms. I understand
the idea that a strategic partnership can add value, but having complete
control of a company is also very valuable, and I don't know why Shaw wants to
just give that away when it would cost him very little to not do it.

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dekhn
It really remains to be seen whether these approaches will make any difference
in efficacy or cost of pharmaceuticals.

Blindly thinking that having better simulations of proteins and drugs is going
to solve any of the hard problems has led to a great deal of waste.

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melling
I’m not sure why you consider it a great deal of waste.

Building better models that simulate a human biological process must have some
sort of payoff? It increases human knowledge, and should provide a foundation
on which others can build.

~~~
jjoonathan
A waste for society? No. A waste for the people doing it who are never going
to be appropriately compensated for the value of their failure to society?
Yes.

The churn that arises as a consequence of the fact that we don't know how to
reward failure (or even merely punish it less) is the real waste.

~~~
vthallam
> A waste for the people doing it who are never going to be appropriately
> compensated for the value of their failure to society? Yes.

Judging by their profiles, I don't think they care if they end up being a
failure with this Venture.

~~~
jjoonathan
Yes, but if the scientific value capture problem were solved then science
could scale appropriately rather than beg for charity.

I was (and would be) much more valuable to society as a structural biologist
than I am as a software engineer, but the market disagrees so vehemently that
it's cost prohibitive for me to fight it, and the result is that we all lose.
The reason _why_ it disagrees is not hard to understand and not particularly
difficult to categorize as a market failure rather than a "hard truth." I
can't really think of a good way to actually address the problem, though, so
mostly this just amounts to venting.

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known
D.E.Shaw was my former employer. I wish him success.

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erikb
The title looks like a really good idea for a modern-world pen&paper RPG
system.

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atrexler
Overload your gels much bro?

JK- just looking for those impurities.

