Physicists offer new theory on cancer
asunews.asu.edu
asunews.asu.edu
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...
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.
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.
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) 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.
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.
The good news is that we already have that data! From 2005.
https://www.ncbi.nlm.nih.gov/pubmed/15920528
And the story, is, of course that it's waaay more complicated than that.
For that matter, we know a lot of cancers (e.g. CML) come about in no small part due to fusion proteins - which would be if anything, the creation of a novel protein, not a gene that is 'deeply conserved'.
I've recently won a hackathon (http://hack4ac.com) with an idea to cut the middlemen out of the science news cycle with only a single link remaining: from the scientist to the general public. It was built to prevent this sort of misinformation, intentional or not. I believe it usually is unintentional and is just a side product of all of the players in the science news cycle playing their part in the game of 'telephone', and information just gets mangled. The project (ScienceGist) puts scientists into the driver's seat of their own communication with the public.
ScienceGist is a < 2 weeks old open source project https://github.com/jure/sciencegist http://www.sciencegist.com looking for contributors who think scientific communication is a crucial problem to solve.
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...) 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.
Seems reasonable to me.
Like rushing to publish your conjecture of the molecular structure of DNA before it's fully verified with crystallography data?
No it wouldn't. Cancer expresses fundamental genes critical to all multicellular organisms. That is already known so the fact that cancer expresses 'older' genes doesn't prove anything.
It is very clear from the press release and also form his own article on his 'theory' from 2011 http://www.guardian.co.uk/commentisfree/2011/apr/25/cancer-e... that he doesn't understand evolution.
Consider this nugget of wisdom that is 100% pseudoscience: A century ago the German biologist Ernst Haekel pointed out that the stages of embryo development recapitulate the evolutionary history of the animal. Human embryos, for instance, develop, then lose, gills, webbed feet and rudimentary tails, reflecting their ancient aquatic life styles.
That is wrong, it has been know to be wrong for a hundred years at least and basing a theory on it is ridiculous.
Scientific consensus believed bleeding patients was a proper treatment for two thousand years.
Things change.
From a common sense point-of-view it still seems like a legitimate theory to me.
No, I think that what the grandparent meant is that, for all the problems "ontogeny recapitulates phylogeny" has, it is quite falsifiable in its claims, and they have been falsified. Therefore, its false.
> Scientific consensus believed bleeding patients was a proper treatment for two thousand years.
"Proper" isn't part of a scientific conclusion, and for most of the time bloodletting was an accepted treatment, the scientific method didn't exist (it certainly hasn't for two thousand years), so it couldn't be the subject of a scientific consensus.
Scientific consensus does change, though, but the important thing is why. A theory which loses status as a consensus not because it has been falsified but because a more broadly applicable or parsimonious (two sides of the same coin, really) theory with equivalent predictions (at least, of those that have been tested) insofar as their domains overlap replaces it might still be correct, even though it is no longer the consensus theory. One that is rejected because its testable predictions have been shown to be false is not in the same position.
> From a common sense point-of-view it still seems like a legitimate theory to me.
A theory that comports with "common sense" (i.e., someone's intuition) but whose claims don't stand up to empirical scrutiny does not remain valid merely because it is (for someone) intuitive.
But getting an idea out there is in any case a net positive.
Scientific breakthroughs don't start with double blind studies; they start with an idea. To say it with Einstein: Imagination is more important than knowledge.
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.
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...
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....)
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.
Of course this is total pseudoscience and I'm floored someone is receiving money for coming up with this. His descriptions of cancer (after two years of apparent study) simply do not make sense in any context.
Cancer's adaptation to anaerobic respiration has been know for a long time and isn't some magical 'atavism' or 'safe mode' but a necessity for a tumor.
and now I'm going to be pithy: Looks like some physicists think oncology recapitulates phylogeny.
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.)
That said, the idea of targeting characteristic differences that show up when those controls are turned off was somewhat novel to me. But I'm not in the field, and that might be old hat as well.
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 ]
But it seems they suggest something, indirectly: go jogging (more oxygen) and ban/reduce sugar consumption.
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.
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.
Relevant SMBC: http://www.smbc-comics.com/?id=2556
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.
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?
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?
http://scienceblogs.com/pharyngula/2012/11/20/aaargh-physici...
[0]http://scienceblogs.com/pharyngula/2011/04/26/aaargh-physici... [1]http://freethoughtblogs.com/pharyngula/2012/11/20/aaargh-phy... [2]http://freethoughtblogs.com/pharyngula/2012/12/19/aaargh-go-...
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
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.
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?
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.