
Physicists offer new theory on cancer - alphanumeric0
https://asunews.asu.edu/20130712_pauldavies_cancer_research
======
tokenadult
Ah, yes, a university press release, with its well known role in the Science
News Cycle.

[http://www.phdcomics.com/comics.php?f=1174](http://www.phdcomics.com/comics.php?f=1174)

I wish these researchers well. Cancer has been tough to treat,

[http://www.sciencebasedmedicine.org/why-havent-we-cured-
canc...](http://www.sciencebasedmedicine.org/why-havent-we-cured-cancer-yet/)

in large part because "cancer" is not really just one disease, but a general
term for a variety of related diseases with many different kinds of outcomes
and treatment trade-offs.

If someone can find a very general commonality to most cancers, with a
treatment for that commonality that is safe and effective (and not too
expensive) for human beings around the world, that person will of course win a
Nobel Prize in medicine. Here on Hacker News, over the 1704 days that I have
been here, I have seen many kind submissions of breathless claims of
breakthroughs in cancer research. We all desire that cancer breakthroughs
happen. Follow-up, so far, has not suggested that any such cancer breakthrough
actually has happened. I wish the researchers well, and I hope to hear later
about placebo-controlled multicenter clinical trials that show that this
approach is safe and effective for human medicine.

~~~
opminion
Hum... the article does not talk about anything that could be _placebo-
controlled multicenter clinically trialled_.

It's just about some dudes deriving conclusions from the relationship between
embryo development and (what they call) cancer, with a couple of predictions
thrown in to make their theory falsifiable. As a press release is not that
bad.

~~~
arkades
"deriving conclusions from the relationship between embryo development and
(what they call) cancer"

Except that they repeatedly say "The new theory predicts that as cancer
progresses through more and more malignant stages, it will express genes that
are more deeply conserved among multicellular organisms, and so are in some
sense more ancient". So, just to be clear, they're not deriving conclusions
from a relationship between embryonic development and (what they call) cancer
- they're deriving a relationship from their conclusions.

Physicists poking their noses into fields they know absolutely nothing about
and making grand pronouncements isn't new.

Why this is a 2013 press release I don't know - they basically published on
this in 2011
([http://iopscience.iop.org/1478-3975/8/1/015001](http://iopscience.iop.org/1478-3975/8/1/015001))
though they seem to be no further along now than they were then - which is
nowhere, since in 2011 they were basically still saying "We think these are
atavistic genes, here is the sort of research agenda that might reveal
this..." and then they didn't undertake that research, as far as I can find.
They're still just speculating on it.

~~~
bobwaycott
Okay, you're right about deriving a relationship from their conclusions. At
least mostly. There's certainly an interesting set of possibilities to be
pursued where the idea is concerned with evolutionary processes and thinking
outside the box of seeing cancer as purely a random mutation, and the
problematic questions Davies and Lineweaver pose from that standing
perspective.

Yes, they are speculating on a potential new direction of study based on being
outside observers who specialize in physical systems and recognizing
orchestrated, systemic actions.

However, let's dial down the disdain slightly, can we? These aren't physicists
arbitrarily and whimsically "poking their noses into fields they know
absolutely nothing about and making grand pronouncements". These are
physicists who _have been asked_ to poke their noses into something they know
absolutely nothing about and help existing specialists uncover potentially new
avenues of research. Davies makes this very clear in his opening statements of
the article. He admits he knew nothing about cancer, and started asking
questions that were not typically the questions asked by standing specialists
--who show a pattern of questioning and investigating cancer from that
perspective of a random genetic mutation that occurs in humans, and not
investigating the possibilities that might be found in questioning cancer as a
feature of multi-cellular life as a whole.

Davies and Lineweaver are not saying this is the fundamental theory of what
cancer is. They are suggesting it as a possibility of future research and
investigation and, given their work in their own fields, I strongly suspect
they'll be willing to update their notions based on evidence.

Who knows where we can get if more respected scientists joined cross-
disciplinary programs that were aimed at collaborating on investigating and
understanding various human concerns. It's not like the physicists who've
joined these programs (of which Davies and Lineweaver are but two) are going
to set back cancer research and treatment.

------
jforman
"Davies and Lineweaver are currently testing this prediction by comparing gene
expression data from cancer biopsies with phylogenetic trees going back 1.6
billion years, with the help of Luis Cisneros, a postdoctoral researcher with
ASU's Beyond Center."

Press releases for untested scientific conjectures (further nerd-rage inducing
by calling it a "theory" in official communication) raises a red flag for me:
it suggests that the investigators aren't fully skeptical of whether their
conjecture actually represents the real world, and increases the probability
that they'll introduce bias in their investigation.

The article
([http://physicsworld.com/cws/article/indepth/2013/jul/01/expo...](http://physicsworld.com/cws/article/indepth/2013/jul/01/exposing-
cancers-deep-evolutionary-roots)) is 100% hand-waving imo:

"Could it be, we wonder, that cancer’s predilection for a hypoxic environment
reflects the prevailing conditions on Earth at the time when multicellularity
first evolved, before the second great oxygenation event?"

"Wondering," alas, is not science! We need a model, a hypothesis, and a well-
controlled experiment to actually discern truth.

~~~
arkades
"Could it be, we wonder, that cancer’s predilection for a hypoxic environment
reflects the prevailing conditions on Earth at the time when multicellularity
first evolved, before the second great oxygenation event?"

Could it be that once cells are approximately 2-3 cell-diameters away from a
blood vessel they die of hypoxia, and thus cannot break through a basement
membrane and achieve metastasis without evolving a tolerance for hypoxia? This
is essentially the cancer-specific version of the anthropic principle.

I love it when physicists start spinning yarns about other people's fields.

~~~
bobwaycott
They are hardly "spinning yarns". Did you miss the part where they were
_asked_ to be part of a cross-disciplinary program, along with other
physicists, to bring fresh ideas to the field of cancer research? They are
doing what they were asked to do, and wrote an article on it. It's hardly a
setup for clinical trials in which human lives are at stake, so I think we
can, while holding out for evidence that increases the probabilities of
certainty in this theory, allow them to do what they've been asked to do.

------
molbioguy
Physicists have made great contributions to molecular biology, but this isn't
one of those cases. This one is so wrong at so many levels it's hard to to
justice to it. Much of it just misinterprets things we already know.

In the article it says:

 _Davies and Lineweaver claim that cancer is actually an organized and
systematic response to some sort of stress or physical challenge. It might be
triggered by a random accident, they say, but thereafter it more or less
predictably unfolds._

There's nothing new here. Cancer is basically deregulated cellular replication
and proliferation. These are core processes in multicellular organisms, so of
course they unfold predictably. The trigger is often a mutation ("random
accident") in a key regulatory gene.

The article says the new theory "challenges the orthodox view that cancer
develops anew in each host". But we know that the mechanism of proliferation
does not develop anew in each cancer; only the trigger is different in
different cancers.

The physicists say _“We envisage cancer as the execution of an ancient program
pre-loaded into the genomes of all cells,” and that "it will express genes
that are more deeply conserved among multicellular organisms, and so are in
some sense more ancient."_

Since cellular replication programs are deeply rooted and ancient because they
are fundamental processes, this shouldn't be surprising.

"Sure enough, cancer reverts to an ancient form of metabolism called
fermentation, which can supply energy with little need for oxygen, although it
requires lots of sugar." Guess they are unaware that your muscle cells do they
same when they are starved for oxygen! Anaerobic "fermentation" is a standard
part of our metabolic system under certain conditions.

This goes on and on...

~~~
nikster
I don't see you pointing out anything that is wrong?!

I also disagree that all that stuff should be obvious to everybody. Certainly
wasnt to me, although it makes sense, which is why it's interesting. Rather
than saying "hell, anybody can get cancer and we have no idea why" these guys
seem to think about its role in evolution. They are thinking about it not as a
random mutation but as an intentional genetic program which just makes much
more sense.

Like in any criminal investigation, answering the cui bono question is
imperative. I agree with the people in the paper actually: A deeper
understanding is necessary. We dont know whether that will lead to a cure but
as a software engineer its my experience that you can't fix a bug you don't
understand. (And it amazes me so many of my fellow engineer try....)

~~~
molbioguy
_I also disagree that all that stuff should be obvious to everybody._

It doesn't. But not everybody publishes something in journals. When you do,
you have a responsibility to know your subject.

 _They are thinking about it not as a random mutation but as an intentional
genetic program which just makes much more sense._

This actually makes little sense to me. The replication machinery and
programming is deeply established, not a random mutation. The mutation is in
the genes that regulate the system. The inappropriate execution of the
replication is the key and that's well established to arise from mutational
changes in regulatory elements.

------
dnautics
As a biologist and chemist studying cancer, this sounds an awful like the
"ontology recapitulates phylogeny" theory which, while a cute just-so story,
turns out to be a particularly misleading way of looking at developmental
biology.

and now I'm going to be pithy: Looks like some physicists think oncology
recapitulates phylogeny.

~~~
btilly
_As a biologist and chemist studying cancer, this sounds an awful like the
"ontology recapitulates phylogeny" theory which, while a cute just-so story,
turns out to be a particularly misleading way of looking at developmental
biology._

It is misleading, but with a small kernel of truth that appears in the
article.

That kernel is that there is little evolutionary pressure to cause changes in
early development, and huge potential consequences to adjustment there, so
early development is remarkably stable across many species. And this
conservation goes right down to the genetic level. Thus it is wrong that we
trace out our evolutionary heritage, however it is true that there are
similarities between early development of distant species, and that
commonality is due to conserved genes that evolved a very long time ago.

(There is, of course, another commonality. And that is the observation due to
Gould in _Ontogeny and Phylogeny_ that a lot of the raw material for evolution
comes from altering the timing and rates of existing development processes,
rather than from introducing "new" features.)

~~~
dnautics
That cancer is predominantly not "just" a mutagenic defect but that it more
specifically recruits developmental controls and make them go go awry is
relatively new in biology, but not revolutionary.

~~~
beagle3
Can you quantify "relatively new"? It was clear to me 10 years ago, and I
thought it was common knowledge, but then everyone I talked to (especially
people from medicine and biology) called it "an novel, interesting theory"
when I talked about it (and had to explain why that would make sense).

If there's a name or reference for this theory, I would appreciate a link.

[ My argument that gets the "novel and interesting" theory remark is that in
many cases cancer becomes "chemo resistant" after much shorter than any
multicellular organism would -- thus, it can't just be a random mutagenic
defect, and must involve non trivial developmental/evolutionary machinery. I
don't remember where I picked it up, and it might have had a different form,
but it was over 10 years ago ]

~~~
dnautics
yeah, that's probably about right. I had first started hearing about it 3
years into grad school (i.e. 6 years ago), and I wasn't really a biologist
with an interest in oncology until recently.

------
nicholas73
I am surprised that the majority of comments ridicule or scorn this idea. I
found it to be at least an explorable link, even if it would yield no
practical cure. It was nice to know which genes are involved, which still
makes no claim on the trigger of cancer. It merely states that forms of stress
could activate this, and this still would be in line with current theory of
one-off mutations (that is, the tangible result after the event).

~~~
novalis78
>even if it would yield no practical cure.

But it seems they suggest something, indirectly: go jogging (more oxygen) and
ban/reduce sugar consumption.

------
riwsky
PZ Myers, a biologist, gives a good reaction to some earlier news on these
physicists at [http://scienceblogs.com/pharyngula/2011/04/26/aaargh-
physici...](http://scienceblogs.com/pharyngula/2011/04/26/aaargh-physicists/)

~~~
anthonyb
I stopped reading PZ Myers quite a while ago - he's almost entirely negative,
and doesn't seem to be able to do much more than flame other people.

eg. his little diatribe on Haekel. Ok, Haekel was wrong, but the initial
processes behind embryo development must still be pretty old, right? Nope,
apparently, even mentioning Haekel == wrong, and your whole argument is wrong
and you're stupid and should be embarrassed, etc, etc.

------
microtherion
Reading that title, I couldn’t help being reminded of
[http://xkcd.com/793](http://xkcd.com/793)

~~~
pedrosorio
My thoughts exactly!

------
jasonkolb
I love the fact that physicists are looking at this problem. I really love the
way they think--that there are underlying elegant solutions to inherently
messy problems. I think it speaks to how much you think the universe makes
sense underneath everything, and they see it on a daily basis. Hence, the
success and reknown of an Einstein for example: someone who takes the
currently-best-known-answers and makes them simpler, more elegant.

I think this sort of thinking needs to be applied in many more fields than it
is, and it's very encouraging to see some people from outside the traditional
medicine groups even looking at this supremely important problem. We don't
need more drug studies, we need more root cause analysis.

------
eridius
A physicist chiming in on matters outside of the field of physics? Why am I
not surprised.

Relevant SMBC: [http://www.smbc-comics.com/?id=2556](http://www.smbc-
comics.com/?id=2556)

~~~
bobwaycott
Chiming in? These physicists were asked to join 12 cross-disciplinary centers
with other cancer specialists, setup by the US National Cancer Institute, and
Davies was asked to lead one such center. He's not chiming in on anything;
he's doing the job he was asked to do.

Whether this theory ever gets beyond discussions with field experts is another
story. But as it stands, he's not just lobbing fly balls to the outfield for
no reason.

------
eclipxe
"This could provide clues to future treatments. For example, when life took
the momentous step from single cells to multicellular assemblages, Earth had
low levels of oxygen. Sure enough, cancer reverts to an ancient form of
metabolism called fermentation, which can supply energy with little need for
oxygen, although it requires lots of sugar.

Davies and Lineweaver predict that if cancer cells are saturated with oxygen
but deprived of sugar, they will become more stressed than healthy cells,
slowing them down or even killing them. ASU’s Center for the Convergence of
Physical Science and Cancer Biology, of which Davies is principal
investigator, is planning a workshop in November to examine the clinical
evidence for this."

This stood out at me as particularly interesting - especially as someone that
tries to limit sugar and carbohydrate intake. I've heard other theories about
sugar helping cancer spread - does anyone have more information or research on
this?

------
bobwaycott
Source article (requires login):
[http://physicsworld.com/cws/article/indepth/2013/jul/01/expo...](http://physicsworld.com/cws/article/indepth/2013/jul/01/exposing-
cancers-deep-evolutionary-roots)

------
swamp40
Is it true that the latest scientific consensus about cancer is that it is the
result of random genetic mutations?

Yet there are only about 200 well defined types of cancer that just appear
over and over again, millions of times per year?

And then someone suggests that the mechanism and progression path might be
embedded into our DNA, and it gets called pseudoscience?

~~~
dragonwriter
No, it is not true that the scientific consensus on cancer is that it is
caused exclusively by random genetic mutations. Different cancers have
different causes. There are, for instance, a small number of viruses that
together cause a sizable fraction of cancers. Viruses make fairly specific
genetic changes.

------
lnanek2
Sounds like they are coming up with testable predictions, so rock on! That's
how it works in physics. Come up with a model, check the predictions, if the
model is nuts but predicts well, you have no choice but to accept it until
something better comes along. See General Relativity and it's bizarre time
space bending and stretching. And Quantum Mechanics. All the biologists going
nuts in this thread sound just like people who couldn't accept things can be
in multiple states at once.

------
selimthegrim
I believe PZ Myers offers the definitive verdict.

[http://scienceblogs.com/pharyngula/2012/11/20/aaargh-
physici...](http://scienceblogs.com/pharyngula/2012/11/20/aaargh-physicists-
again/)

~~~
fernly
Myers visits the Davies/Lineweaver speculations three times, in April 2011
[0], November 2012[1], and December that year. PZ is quite scornful in all
three posts, but after all, he is a biologist specializing in developmental
biology -- so he can be assumed to know the literature, and the details of
cell biology, which he claims they very clearly do not.

[0][http://scienceblogs.com/pharyngula/2011/04/26/aaargh-
physici...](http://scienceblogs.com/pharyngula/2011/04/26/aaargh-physicists/)
[1][http://freethoughtblogs.com/pharyngula/2012/11/20/aaargh-
phy...](http://freethoughtblogs.com/pharyngula/2012/11/20/aaargh-physicists-
again/) [2][http://freethoughtblogs.com/pharyngula/2012/12/19/aaargh-
go-...](http://freethoughtblogs.com/pharyngula/2012/12/19/aaargh-go-away-
silly-physicists/)

------
aheilbut
This doesn't really sound like a completely new theory; Haeckel proposed in
the 1800s that "ontogeny recapitulates phylogeny", and it is widely understood
that cancer is like a de-differentiated state.

------
bobwaycott
From the source, Davies' argument (for those who don't want to register for
_Physics World_ ):

Cancers prevalence among multi-cellular organisms indicates it is "deeply
embedded in the logic of life". It is found among mammals, birds, fish,
reptiles, and other organisms. The human genome is pre-loaded with a "cancer
sub-routine" that is triggered by various factors. Once triggered, most
cancers follow a similar pattern: reproduce uncontrollably in a specific
organ, then spread throughout the host, invading and colonizing other organs
and parts of the bodies with the help of tumors.

> _The overall impression is of a carefully orchestrated and pre-programmed
> strategy--its aim to multiply cancer cells and colonize new sites--which is
> unleashed when neoplastic cells somehow evade the normal regulatory
> mechanisms of the organism and embark on their own agenda._

Seeing a "highly organized and efficient behaviour in biology" leads Davies
and Lineweaver to suspect evolutionary mechanisms at play. Davies finds that
orthodox explanations describing cancer as random genetic mutations starting
from scratch leave too many unanswered questions--such as why they are fitter
than the existing healthy cells in a body, why such random mutation provides
"a whole series of mutually supportive survival traits ... in a period of just
years of months", why dormant cancer returns in the same organ after a primary
tumor is removed, or "why cancer cells deliberately transplanted into certain
tissues, or cancer nuclei into healthy cells, often results in normal
behaviour", while the reverse process results in cancerous cells.

Thus, from a physics perspective, "there are clues pointing to cancer as a
phenomenon influenced by forces and fields--not one that is purely ruled by
genetic instruction." Sadly, the article never dives into more on this physics
perspective and what kinds of forces and fields may be at play, instead
turning to evolutionary biological arguments from embryonic development
applied to cancer development.

> _Cells are usually regulated by mechanisms that instruct them when to
> multiply and when to die. What we believe is that when these mechanisms
> malfunction, the cells revert to the default option, a genetic subroutine
> programmed into their ancestors long ago, of behaving in a selfish way._

> _Lineweaver and I suggest that genes that are active in early-stage
> embryogenesis and silenced thereafter – which, by our hypothesis, are
> generally the ancient and highly conserved genes – may be inappropriately
> reactivated in the adult form as a result of some sort of insult or damage.
> This trigger serves to kick-start the cascade of maladaptation events we
> identify as cancer. So the "cancer subroutine" is really just a re-run of an
> embryonic developmental program. We envisage a collection of ancient
> conserved genes driving the cancer phenotype, in which the metastatic
> mobility of cancer cells and the invasion and colonization of other organs
> merely reflects the dynamically changing nature of embryonic cells and their
> ability to transform into different types of tissues._

> _The big picture is that we attribute cancer 's survival traits to deep
> evolution on a billion-year scale, rather than orthodox explanations that
> point to evolution from scratch with each case of the disease. In our
> theory, the latter remains true, but is a small perturbation._

The ASU article covers much of the rest of the original article by Davies. ASU
just left out much of the lead-up to how they arrived at their conclusions.

 _Physics World_ also has a lot more coverage in the current issue, entitled
"Physics of Cancer". The entire issue can be downloaded as PDF here:
[http://physicsworld.com/cws/download/jul2013](http://physicsworld.com/cws/download/jul2013)

------
teekert
Well, as a molecular biologist I can't say I ever saw cancer in any other way.
What's so new about this?

We all know that embryonic, proliferation and stem cell associated pathways
like the Wnt pathway and the PI3K pathway commonly are the ones that get out
of hand in cancers. We also know that proliferation in single cells is the
highest goal and that the uncontrolled division of a single cell (as it
probably did when still living alone) leads to problems in higher organisms.
If the fail-safes that developed to allow for multicellular organisms fail to
prevent the egocentric behaviour of individual cells and a cell reverts back
to a "divide as fast as you can"-state, they become what we call cancer cells.

I fail to see the news value in this article.

------
IgorPartola
Odd. I always assumed that cancer was a natural part of a living organism, and
that what got disrupted was the "cancer suppression mechanism" (not a
technical term). The fact that cancer evolves anew in every patient seems
very... improbable.

~~~
bobwaycott
Yeah. Similarly, I pretty much landed (around a decade ago) on seeing cancer
as little more than a small subset of death for which we'd identified features
and given it a name--i.e., before humans identified cancer, people just died
for then-unknown reasons (which were likely, at given points in history,
called 'natural causes'). Once we identified cancer, people 'got cancer' and,
subsequently, a varying percentage of such people died, with that percentage
declining as understanding and treatment improved. I remain fascinated by
cancer research and the hope for a cure because I remain fascinated by seeing
humans practicing science discover more ways to identify death and prevent it.

------
mathattack
I get nervous when physicists wander too far from Physics. They're a smart
lot, but look what happened when they went into Finance. :-) It takes a while
to apply the math skills properly elsewhere.

------
gonzo
ho-hum newbie-think

consider the source

"Arizona State University Regents' Professor in ASU's College of Liberal Arts
and Sciences. “It is rather like Windows defaulting to ‘safe mode’ after
suffering an insult of some sort.” <snicker> It's probably as attractive and
simplistic as the old saw "ontogeny recapitulates phylogeny". Kinda true at
some levels, but not really. Sometimes functionally useful. Certainly not new.
Wanna contribute to ASU? Have I got a real smart guy for you..... Or is that
the London Bridge in Arizona?

------
stephengillie
Off-topic: Does it bug anyone else that this guy's desktop is 3/4 covered in
icons?

~~~
swamp40
That's what my desktop looks like.

I use it to store any file that I save because it's the first spot that pops
up (and the easiest one to find no matter where you are) in Windows Explorer
or when you right click and say "save as".

Then every few months I shove them all into an "old desktop" folder.

The horror.

------
jlebrech
if you turned the gene off would you be able to have kids though?

------
lvs
This bullshit is bullshit incarnate.

