
Cancer Isn’t a Logic Problem (2017) - signa11
http://cancer.nautil.us/article/186/cancer-isnt-a-logic-problem
======
travisoneill1
> Systemic approaches are important, but we need to consider that the system
> of cancer goes far beyond the biochemistry of cancer cells. Cancer relates
> to our fundamental constitution as multicellular organisms, our limited
> lifespan, the epidemiology of the aging population, socioeconomics and the
> future of society. Those who believe that the problem of cancer can be
> solved by killing or reprogramming cancer cells need to take a step back
> from the molecular technicalities and take a look at the bigger picture

He knows that this approach won't work before it has been attempted? I'll
listen to criticism when it is followed by a suggestion for a better approach.
And vacuous statements like "step back and look a the bigger picture" don't
count.

~~~
pesmhey
The ability to actually reprogram cancer cells relates to...

>our fundamental constitution as multicellular organisms, our limited
lifespan, the epidemiology of the aging population, socioeconomics and the
future of society.

Like, hey man, you do realize that the killing or reprogramming of cancer
cells goes far beyond the molecular technicalities of actually doing it?

Yup. It’s a pretty vacuous critism.

~~~
devereaux
Medical technology is lacking. With sequencing, we have a very hard-to-use,
slow and readonly hexedit. With crispr, we have a very buggy and feature
incomplete sed -- more like ed actually.

It cool to have some sed, but we may not even need that. We just need the
equivalent of basic modern unix tools, like find, grep and rm, that work
reliably, with good specificity and sensitivity.

Yet basic unix tools in medicine are decades away. Maybe it will be
nanotechnology, maybe it will be more hacking around current solution.

Still, the problem is just:

find /body -type cancer_12BA |grep -v cancer_12BA_market_but_usefull_stemcell
|xargs rm

The solution is technological, not philosophical.

~~~
Wowfunhappy
Your crispr = sed analogy is apt because DNA is basically code.

Cells, however, are not files, so I would be careful extending the analogy.
There is no "find" command for the same reason you can't run "find" on your
physical bookshelf--objects in 3d space are not indexable files on a hard
drive.

Perhaps we'll eventually have microscopic robots that can search out specific
cells, in the same way Amazon uses robots to retrieve items in their
warehouses. But that's a very different problem space, where the focus is
largely mechanical rather than programmatic.

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dannykwells
As someone who works at a place mentioned in this article, I can tell you, we
do not subscribe the belief set he says we do, and actually, likely agree with
the author that cancer is a systemic disease that involves not only the tumor,
but also the TME, the peripheral immune system, other organs, etc. The "tumor
only" view of cancer is dead and has been very a while, and even "Silicon
Valley" knows this.

Also, for those here: checkpoint inhibitor therapies are a "better approach"
that incorporate a systemic activation of a patient's immune system to kill
cancer, and they really, really work (see: Nobel Prize this year to Jim
Allison).

~~~
shaneofalltrad
This is also not perfect, as for example those with autoimmune conditions will
not always work and can actually get worse under immunotherapy. My wife has
stage 4 lung cancer due to Scleroderma immunosuppression medication and is
struggling with the treatments due to the reactions ( immune system attacking
non cancer cells ).

~~~
randcraw
As a cancer survivor, my heart goes out to you both.

As someone who also works for a company that makes a checkpoint inhibitor, one
of our chief efforts is to better understand what makes them work for some
patients and not others. Not only would this knowledge serve the lucky
patients by tuning their therapy for better efficacy and lesser side effects,
but would help us know more about how CPIs fail, and ideally, to enable their
use in the many, as yet, unlucky patients.

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TaupeRanger
The article is really bad. What is preventing nanobots, for example, from
completely eradicating the problem of cancer at some stage of technological
development? It's like the author wants cancer to have some mystical power
over us forever and is fitting all current endeavors to that narrative.

~~~
dekhn
I'd say the article is realistic, based on how oncology is currently done in
the medical field.

As for the question of whether nanobots can completely cure cancer, that's
scifi. Actually identifying tumors and removing them is a hard classification
problem followed by a careful surgery. Generally this is done using advanced
imaging, radiologists who interpret the images, guiding surgeons or doctors to
either do tumor resections, or select chemotherapy. Nanobots are just a tiny
version of the tumor resection, with the added problem that nanobots don't
exist, they don;t' have the computational power to discriminate invasive
tumors (at least, the current generation of "robot pills don't).

So let's focus on what is tangible in the near future: additional use of
machine learning based on large training sets collected across hundreds of
studies. That is in fact very likely to counter the author's hypothesis.

~~~
esahione
It is sci-fi just like having the entire world's knowledge at your fingertips
was sci-fi 100 years ago.

If it is physically feasible, which it is given we have immune cells and they
are just evolution-created versions of these nanobots, then it is just an
engineering problem and we humans are pretty good at engineering things.

Things will keep moving forward; macro approaches such as your suggestions
will work insofar as we can find the cells. In the end it will probably be a
mixture of re-engineering our immune cells to better identify and protect
against cancer, macro approaches such as the ones you mentioned, and more.

It is a hard problem, of course, otherwise we'd have it solved by now, but
we've solved hard problems before. And with AI it will be easier and easier to
do so.

~~~
dekhn
you know I've worked in this field for over 25 years and while I started out
thinking nanobots were going to cure diseases, I haven't seen any realistic
evidence showing they have a promising future, even 100 years from now. I
think it;'s much more likely we'll just study immune cells more and use them
for therapy without creating nanobots.

~~~
JumpCrisscross
> _I haven 't seen any realistic evidence showing they have a promising
> future_

We’re not yet at nanoscale manufacturing in one of the few domains with the
scale and capital to fund its development: microprocessor manufacturing.

~~~
Retric
What do you think editing DNA to make a protean is? You don’t get smaller
scale than individual atoms, but it takes more than an atom to do anything.

~~~
JumpCrisscross
> _What do you think editing DNA to make a protean is?_

Re-defining biology as “nanobots” renders the latter word useless.

~~~
Retric
Biology runs on the same physics as anything else. At best nanobots get a
wider range of atoms to play with, and that’s it.

~~~
JumpCrisscross
> _Biology runs on the same physics as anything else_

Paper planes and fighter jets run can be modelled by the same physics. That
doesn’t mean they’re the same thing. “Nanobots” implies greater degrees of
freedom and function than purely biological techniques can manage. (For
example, by incorporating digital circuitry and novel materials into the mix.)

~~~
Retric
Nanomachiens are to small and fast for digital circuits.

As I said, they can include more types of atoms, but that adds little as life
already makes use of a wide variety. It’s basic capacity that’s the issue not
micro optimizations. Further, depend on a non organic atom and you can’t self
replicate without being fed it.

At the smallest scale you can’t for example take a picture, you need to detect
stuff by touch and respond before bouncing off while traveling at 50+MPH. Make
a vast structure like a cell and movement and energy become major issues.

~~~
JumpCrisscross
> _Nanomachiens [_ sic _]are to small and fast for digital circuits_

“Digital” means a logic model. Not a physical technology. Atomic-scale digital
circuitry—completely foreign to life as we know it—is certainly plausible.

Your claim is that anything that can be done at the nanoscale can be done by
“editing DNA to make a [protein].” I’m saying the latter is a subset of the
former. Given all we have, at this point, is theory, it’s a reasonable point
on which to disagree.

~~~
Retric
I get what you mean by digital, the problem is analog is _vastly_ faster and
more compact. Digital essentially reduces the solution space adding overhead.
It’s not a technical problem it’s the core tradeoff for going digital.

That’s not to say proteins are as efficient as possible. Just that they are
fairly close to the limit of what’s possible at 1 to 100nm. Now start talking
micrometers‘s and I can see some things changing.

------
antoniuschan99
Really interesting article.

Cancer is definitely shapeshifting and it's a constant battle on all fronts.

One drug may work now (eg. anti folates) but then remission fails and it's
back to the fight.

The primary tumor may go into semi-remission but mestasis may happen then you
have to treat that instead.

The tumors suck so much energy from the person's body so it can attack on that
front too.

I think immunotherapy is the future and am really sad that it is so expensive.
It's like Elysium, Keytruda is ~$400k it's sad how costly these drugs are.

I think diet, environment, and habit are the things that have the most effect
over time because it's really just your cells multiplying in an uncontrollable
rate and the body cannot stop the function or the garbage collectors are
unable to make the cell perform aptosis.

There are many things that go in and out of your body over time that will help
increase or decrease the amount of these types of cells that are produced.

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signa11
fwiw, there is an excellent (pulitzer prize winning, fwiw) book called "The
Emperor of All Maladies" by Siddhartha Mukherjee which gives history of cancer
treatment and research, coupled with author's experience as an oncologist.

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csense
The author seems to think there's a certain class of researchers with software
backgrounds who want to cure cancer; have the hypothesis that cancer is,
always and everywhere, a purely genetic phenomenon; and enshrine this
hypothesis as indisputable fact ignoring all evidence to the contrary. This
seems like a straw man.

------
elorant
[https://xkcd.com/1831/](https://xkcd.com/1831/)

~~~
umvi
On the flip side, sometimes people are able to solve a hard problem simply
because they weren't tainted into believing it's impossible. [1]

[https://en.wikipedia.org/wiki/George_Dantzig#Mathematical_st...](https://en.wikipedia.org/wiki/George_Dantzig#Mathematical_statistics)

~~~
throwawayjava
The George Dantzig case actually isn't a counter-anecdote to the XKCD
observation, because Dantzig was already a graduate student in a phd program
at a top statistics department when he solved those problems.

XKCD isn't criticizing the positive mindset of naive-but-gifted researchers;
it's criticizing the attitude of experts in one field that their expertise
necessarily gives them unique and powerful insights into solving problems in
another field.

Perhaps a better counter-anecdote would be all of the mathematicians in the
1950s - 1980s who solved hard program design problems with little or no
experience actually programming computers. That really was a counter-example
to the XKCD mentality: a bit of mathematics was far more useful than knowing
the instruction set of the latest IBM mainframe...

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ciconia
If all you have is a hammer, everything looks like a nail.

I would argue that one of the biggest barriers to fighting climate change is
the blind belief in technology as _the_ solution to any problem facing
humanity. In many ways it is a cult. But in order to fight climate change we
might need to turn to simpler, more low-tech solutions.

I mean, we're spending all that effort flying to the moon and trying to
program cancer cells, while all we really should do to fight cancer is clean
up the air we breathe, stop spraying pesticide on our food and lead less
stressful lives. Just saying...

~~~
bobjob
That is not how cancer happens. Cancer happens because we live and some
factors make it more likely that cancer happens. But even in a clean world we
would get cancer...

And btw., how would you clean up the world?

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reasonattlm
Cancer research largely proceeds in the wrong direction, towards ever more
personalization to mechanisms specific to one tiny fraction of cancer types,
or tiny fraction of tumors in that cancer type. Then people are surprised at
the low cost-effectiveness of the expenditure. Which is not to mention that
cancers will cheerfully evolve around an attack on any mechanism not vital to
their operation.

Insofar as anything needs hacking, it is this wasteful focus in the research
community. The research community needs a dramatic refocusing onto mechanisms
that cannot be evaded and which occur in most or all cancers. The canonical
example is to interfere in telomerase and ALT telomere lengthening. That can't
be evaded, and all cancers do it. Shut these things down and cancer stops. Any
cancer, any type, any stage, using exactly the same therapy. Yet the amount of
work in this area is tiny in comparison to projects that verge on personalized
medicine per tumor.

~~~
azeotropic
<quote>The canonical example is to interfere in telomerase and ALT telomere
lengthening. That can't be evaded, and all cancers do it.</quote>

Yeah, and so do adult stem cells. As long as your patient doesn't need
intestinal walls, skin, or blood, this will be a totally successful treatment!

Have you entertained the hypothesis that people studying cancer might know
more about biology than anti-aging cranks?

