
Before cancer kills, it cheats - chmaynard
https://news.harvard.edu/gazette/story/2018/04/harvard-talk-envisions-path-to-containing-cancer/
======
wgerard
Hah! Wow that's a blast.

I used to work at a lab as an undergrad that worked on extremely similar
topics, though the cancer link was more implied:
[http://research.fhcrc.org/shou/en.html](http://research.fhcrc.org/shou/en.html)

We had four yeast systems: Two cooperative yeast systems (exchanged
metabolites the other needed to survive), and two cheater systems (needed
those same metabolites to survive, but just took from the system and never
gave back).

One experiment I assisted with was basically putting them all together at
differing ratios and seeing what happened over time - the different systems
released different fluorescent proteins, so we could measure their relative
populations.

Common sense might dictate that the cheaters would rapidly outgrow the
cooperators and eventually crash the whole system, but that actually didn't
happen until very high ratios of cheaters.

The cooperative yeast systems somehow managed to extinguish the cheaters
pretty consistently (all the experiments were repeated and done in
triplicate). This happened even at fairly absurd ratios like 3:1
cheaters:cooperators. Unfortunately, I left before any of the follow-up work
to determine why that was happening.

All that to say, it's fascinating how much cooperative systems really are
favored in nature. Glad to see someone explicitly applying this idea to
cancer.

~~~
QML
Your post kind of reminds of two other articles along the same concept: [1]
[http://ncase.me/trust/](http://ncase.me/trust/) [2]
[https://www.quantamagazine.org/how-to-triumph-and-
cooperate-...](https://www.quantamagazine.org/how-to-triumph-and-cooperate-in-
game-theory-and-evolution-20171109/)

------
bhickey
Slime molds are another excellent model for studying cheating. They're
typically single cell organisms except when starved. Then they chemotax an
aggregate into a multi-cellular organism. At this point they undergo
sporulation, producing a stalk and a fruiting body. Cells in the stalk die
while those in the fruit are hopefully whisked to greener pastures. When the
slimes are homogeneous this works just fine. In a heterogenous setting all
bets are off.

Cheater mutants have been widely observed and fall into two categories:
obligatory and opportunistic cheaters. The obligatory cheaters refuse to
participate in the stalk, while the opportunistic cheats preferentially
segregate themselves into the fruit. It's easy to see how these behaviors
might be beneficial. There's a double edge to obligatory cheating, though: in
they cannot undergo sporulation.

~~~
AllegedAlec
Maree and Hogeweg did some really cool research on Dictyostelium (one of those
slime molds). For those interested:
[http://www.pnas.org/content/98/7/3879](http://www.pnas.org/content/98/7/3879)

------
domnomnom
Here are some ideas:

Look at the functional call stack. Its a slice of the linear address space
that’s actively being used and it is strikingly similar to the promoter
regions of the genome. Like some pathogens, hackers randomly try to hit that
sweet spot that will jump to the special program.

Operating systems are like simple biological organisms that evolve in response
to various influences (cybersecurity it seems these days). My favorite is
OpenBSD, they invent the cybersecurity. They were one of the first to
implement address randomization for kernel and library loading. This is
actually strikingly similar to what goes on with the genome with
retrotransposons during early embryology stages.

People really like to repeatmask (aka SINE/introns) genomes because it makes
BLAST go faster. Ironically, arithmetic/statistical compression algorithms
work really well with repeats (I don’t think this compressed state can be
examined, but compression algorithms are seriously under appreciated).

~~~
smallhands
I have no idea what you are talking about but does human biology have
computation at the core? Any papers on these?

~~~
thraway180306
_biology have computation at the core?_

Doubtful. You can to computing _with_ DNA
[http://dna.caltech.edu](http://dna.caltech.edu) but it is still debated if
the actual role of DNA is being a code (some recently weasel out form that
stance by saying it's an “app”, like there's a difference, machine code being
a code). Coding theory applied to DNA yields inconclusive results. Galois
theory usually has power over any kind of information encoding, cryptographic,
computable or not. One constructed one for DNA convinced mathematicians it's
not the way to go at all. If it's computation it's nothing like what we mean
by any model computation, you may as well say it's magic instead of making
stretched analogies.

About OpenBSD and evolution, that's so fetch... these folk _invented_ the
attack in the first place, not evolved a response to some market force in the
early oughties. Broadly I don't think designed systems are in business of
evolving, otherwise living organisms could perhaps evolved electro-hydrostatic
instead of hydraulic power system with a pump being a single point of failure.

~~~
Cybiote
Linking biology to specific concepts in computer architecture or worse, with
OS design, is indeed a stretched analogy but biology is rich with computation.
I'll try to be short.

A cell must sense and respond to its environment. One aspect of this is
regulation of gene activity by interactions of for example, transcription
factors. When interaction types can be well enough approximated as either of
inhibition or activation, you can model them with boolean networks and when
levels matter, some have found moderate success with recurrent neural networks
under a restriction on what NN nodes represent, to ease interpretability.

That is not the same thing as saying your genome unrolls neural networks. What
it is actually saying is that the complexity of the best performing neural
network indicates the richness of the underlying computation, and the
predictive accuracy of the model captures the functional equivalence of the
respective computations (in the cell and in the neural network). The learned
model is the instance and neural networks are the class, it is a mistake to
place emphasis on neural network, they are merely a way of packaging the
computational model of interest.

A cursory review here:
[https://www.sciencedirect.com/science/article/pii/S001048251...](https://www.sciencedirect.com/science/article/pii/S0010482514000420?via%3Dihub)

If you have time for videos:
[https://www.youtube.com/watch?v=vA9D727AGHI](https://www.youtube.com/watch?v=vA9D727AGHI)
, [https://www.youtube.com/watch?v=ZX-
GrO2qXQM](https://www.youtube.com/watch?v=ZX-GrO2qXQM)

More relevant to this article is the study of cancer within the framework of
_evolutionary game theory_ , as done here:
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768082/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768082/)

There is a precise correspondence between that formulation and one done in
terms of online sequential prediction or the so called experts algorithm. All
of these are models and still quite limited at that but biology is complex and
the future lies in the development and leveraging of these rich connections.

~~~
domnomnom
Can you explain how the analogy is stretched? It’s my personal belief that
biologists tend to be fairly implementation focused from how they learn about
the systems involved.

In biology there is 2 factor authentication to protect against parasitic
spoofing, intrusion detection systems, protected kernel memory, memory
hierarchy, policy based permission. It a very nice operating system IMO.

~~~
Cybiote
Analogies can help but if taken too far, will provide only illusionary
knowledge from superficial similarities. Consider, if you trace out the
hierarchies induced by interactions in biological networks and then do the
same for an OS's call graph, you find quite different topologies reflecting
their different priorities. In computers, in part, efficiency and reuse. In
biology, robustness, minimized interdependencies, developmental stability and
more.

There are things that concern our electronics that do not matter for biology
and there are many things biology must allow for that our hardware cannot.
Tying things down to the peculiarities of our systems too narrows the scope of
applicable models and understanding. Sometimes it is more useful to think in
terms of stochastic differential equations than in terms of operating systems.

------
mikepetroff
A video of her full talk is available here:
[https://www.facebook.com/harvardmuseumsofscienceandculture/v...](https://www.facebook.com/harvardmuseumsofscienceandculture/videos/815475351995720/)

~~~
fredsted
Youtube link:
[https://www.youtube.com/watch?v=NLgvdS3VEQk](https://www.youtube.com/watch?v=NLgvdS3VEQk)

------
homero
A future where cancer is controlled but not cured is just as good and might be
easier to achieve. I hope science gets there before I get cancer which is
inevitable, unless I die from a heart attack.

~~~
jcims
Agreed. My wife is going through this now, and the primary issue is the
uncertainty around it all. Nobody can tell her what her future holds, just
that there's a very high likelihood that 'success' will be fleeting and this
won't be our last series of chemo.

I may be misunderstanding what the author proposes, but if the threat of
cancer was reduced to the physiological impacts of dormant tumors, I'm pretty
sure we would consider that a win.

~~~
spyspy
Always relevant xkcd [https://xkcd.com/931/](https://xkcd.com/931/) really
helped visualize for me what going through cancer treatment is like. God
speed.

~~~
jcims
This pretty much nails it. Thank you.

------
artsnail
How accurate is the comparison with plant fasciation, for anyone who knows
more? My experience with owning/growing fasciated succulents (usually referred
to as "crested" by growers and collectors) has been that they're more
challenging to grow in terms of risks of things like overwatering, but as far
as I know that behavior doesn't necessarily impact their overall lifespan.
Sometimes a crested specimen can also revert back to normal growth. Maybe
that's tangential to the article itself, but it's something I'd be curious to
find more information about.

------
untilHellbanned
Professor at a med school here.

Regardless of whether you think the specifics presented in this article (e.g.,
NSAIDS-esophageal cancer) are right, it’s great to see this kind of
philosophical approach to biomedical research. We need more people like this
professor.

That she started with a plant and that made her think about humans was a great
insight. She rightly recognizes the key role of cell autonomous vs. cell non-
autonomous processes in how multicellular organisms work.

That she is a woman and someone not at an Ivy League school is also very
refreshing to see getting publicized by Harvard. There are so many great
scientists aground the world doing great stuff. Let’s keep finding them and
reporting on them!

Please media, more of these types of stories and less clickbait please! I
loved this article. My faith in humanity was restored just a touch here.

~~~
klmr
> She rightly recognizes the key role of cell autonomous vs. cell non-
> autonomous processes in how multicellular organisms work.

This is an odd comment: This realisation is quite literally at the core of
cancer research, and _every researcher in the field_ recognises this. Heck,
it’s implied if not mentioned outright in the seminal _Hallmarks of Cancer_
paper [1] that every cancer researcher (and probably generally most human
biologist) has read.

Don’t get me wrong: it’s a well-written article explaining the biology to a
lay audience. But it doesn’t hold any striking new insights. All of this is
not merely known but in fact fundamental knowledge.

[1]
[https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer](https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer)

~~~
tcj_phx
> But it doesn’t hold any striking new insights. All of this is not merely
> known but in fact fundamental knowledge.

A lot of "fundamental knowledge" in medicine is wrong. The genetic theory of
cancer has always been a dead-end, because it reverses cause and effect. The
cancer industry has encouraged "kill all the cancer cells" treatments because
it's convenient for their business model. The cancer treatment situation is
similar to how the use of bloodletting persisted for hundreds of years [0], in
spite of the low rates of success.

[0] [http://www.nbc.com/saturday-night-live/video/theodoric-of-
yo...](http://www.nbc.com/saturday-night-live/video/theodoric-of-
york/n8661?snl=1)

There's no need for new insights, the old insight needs to be fully developed.
Your link has a subsection:

[https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer#Deregu...](https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer#Deregulated_metabolism)

Warburg's nobel prize was in 1931; we're finally realizing he was probably
right all along.

(minor edit)

~~~
epmaybe
Your comment is misleading. Certain cancers are indeed 'caused' by genetic
changes, and researchers are actively looking for ways to prevent those
genetic changes from occuring in the first place. But do you really tell
someone with a familial mutation that we know causes thyroid cancer that they
should be on a ketogenic diet?

Most therapeutics today are developed knowing that they will not have a
substantially more beneficial effect than current therapies. We still develop
these because even if they are not better they could reduce adverse events
caused by our current best meds.

As far as I can tell in the last 80 years the Warburg effect has led PET
scanning a viable way to detect the progression of many cancers.

To suggest that increased research into the Warburg effect is going to be the
thing that leads to an explosion in novel therapeutics for cancer is wishful
thinking, as far as I'm concerned. Cancer is complex, and while we could stand
to learn more about metabolic changes in cancer, there's not going to be a
magic pill for this one.

~~~
tcj_phx
Your comment history suggests that you've been through medical school.

I like to say that sometimes doctors do good work, and sometimes they make
work for themselves. Please take this response as a gentle and well-intended
effort to protest the standard practices that hurt patients by 'missing the
forest for the trees', such as I've observed in my own family (who themselves
are employed in the conventional approach to medicine), and my girlfriend (who
is being harmed by allopathic psychiatry).

Did you know that the term 'allopathy' was coined by a homeopath? At the time
bloodletting, calomel, and blister agents were the standard of care.
Homeopathic medicine held that the body can fix itself when properly supported
(diet, clean environment, etc). Allopathic medical practitioners engage in the
heroic struggle against disease [0].

[0]
[https://en.wikipedia.org/wiki/Heroic_medicine](https://en.wikipedia.org/wiki/Heroic_medicine)

Allopathic medicine never went away, it just changed form. While conventional
medical practitioners are doing much better than 200 years ago (w.r.t. not
killing their patients), from my perspective, conventional psychiatry and
conventional cancer treatments leave much to be desired.

> To suggest that increased research into the Warburg effect is going to be
> the thing that leads to an explosion in novel therapeutics for cancer is
> wishful thinking, as far as I'm concerned.

I have some great anecdotes about cheap metabolic therapies. But they're just
my non-rigorous anecdotes... The one person who I'd most like to experiment
on, trusts her doctors because they wear the halo of 'conventionality'.

> Cancer is complex, and while we could stand to learn more about metabolic
> changes in cancer, there's not going to be a magic pill for this one.

Consider the possibility that cancer is much simpler than the geneticists have
led us to believe. Sometimes 'we must unlearn, what we have learned'.

Edit: google scholar turns up some papers about 'spontaneous remission' of
cancer. To figure out how to induce spontaneous remission of cancer cells
would be a revolutionary advance.

~~~
leereeves
> To figure out how to induce spontaneous remission of cancer cells would be a
> revolutionary advance.

There's a lot of work being done on that front, primarily in the form of
inducing an immune response to cancer.

This work is being done in "allopathic" medical schools and hospitals and in
biology labs that are the source of most allopathic medicine.

If this work succeeds, it might lead to a cancer vaccine: the kind of
treatment sometimes opposed by homeopaths and naturopaths.

~~~
tcj_phx
> This work is being done in "allopathic" medical schools and hospitals and in
> biology labs that are the source of most allopathic medicine.

'Allopath' is considered a derogatory term by the modern doctors who are aware
of its origin.

> If this work succeeds, it might lead to a cancer vaccine: the kind of
> treatment sometimes opposed by homeopaths and naturopaths.

The core of the resistance to vaccines is an opposition to the idea that a
disease's context doesn't matter. Improved sanitation, refrigeration, insights
into adequate nutrition, and other improvements in technology have done just
as much as vaccination to vanquish the diseases of antiquity.

~~~
leereeves
> Improved sanitation, refrigeration, insights into adequate nutrition, and
> other improvements in technology have done just as much as vaccination to
> vanquish the diseases of antiquity.

I don't understand the relevance. Will sanitation, refrigeration, or nutrition
protect you from polio, measles, or other diseases commonly vaccinated
against?

------
danharaj
> This is what cancer cells do: Proliferate without limit, avoid cell death,
> monopolize resources, co-opt the labor of other cells, and destroy the
> surrounding environment.

Rings a bell

~~~
gshubert17
Agreed. What can society, which creates corporations, do to limit the
likelihood that they will "go rogue" to harm society?

~~~
wobbly99
Regulate them, limit them and in extreme cases kill them. And the thought that
corporations are cancers of human societies that cheat is not a new.

~~~
2chen
Corporations are more multicellular organisms than cancer. They are capable of
achieving far more than a single cell or person, for better or for worse.

------
aszantu
[https://ketogeek.com/blogs/news/episode-20-dr-thomas-
seyfrie...](https://ketogeek.com/blogs/news/episode-20-dr-thomas-seyfried)
coincidentally listening to that right now

