A blog about science, medicine, media and the ramblings of Irish hack....

Tuesday, March 4, 2014

Tumour spheroids, global warming, homosexuality and motivated reasoning - a somewhat discombobulated research and writing update

 Just a very quick short post of what has been going on lately.. promise you there's a dedicated proper piece on a stand alone subject that should make an appearance later this week...until then, enjoy this somewhat eclectic assortment of subjects

When I logged into write this post, an embarrassing statistic hit me; it's been almost 6 months since I've actually posted something here. I won't insult your intelligence by stating  yet more reasons for my inconsistent posting patterns - my constant flimsy excuses for tardiness transports me back to my teenage days, concocting yet another convoluted excuse for why I had done precisely zero homework, a policy that worked solely because most teachers eventually gave up in exasperation and just stopped asking me.  

Despite the radio-silence here,  I've been relatively productive, juggling irons in a fire whilst mainly avoiding burning my fingers. So in no particular order, a little bit on tumour spheroids, motivated reasoning, climate change denial, self-delusion and the same sex marriage debate! 

(Admittedly that's a slightly jarring combination of topics, but I will endeavour in future to confine each post to a particular topic - stand by later this week for something specific!)

1. Oxygen modelling in multi cellular tumour spheroids 
When I'm not incurring the wrath of the Christan right, the paranoid left, conspiracy theorists, free-market disciples and quackery peddlers I do quite an amount of science. In fact, I even use science as a verb - "I science a lot".  In January we published a paper in Royal Society Interface on oxygen dynamics in tumour spheroids.

So what does this mean? In cancer, oxygen plays an incredibly important role - cancer can be viewed as defective mutant cells dividing utterly out of control, and as a result tumour regions with poor oxygen occur when the cells grow haphazardly. Poorly oxygenated (or hypoxic) tumour regions become far more resistant to both chemotherapy and radiotherapy, and conversely well oxygenated areas respond better. We're interested in modelling how oxygen diffuses through tumour tissue as a "map" of the underlying oxygen distribution would help better inform treatment strategy - essentially, if one had a map of oxygen, then it follows that you could boost dose or treatment to the regions that needed it most.

To model how oxygen diffuses through tumour tissue,  we looked at the simplest possible 3D case, a tumour spheroid - these are "balls" of tumour cells which divide aggressively until they run out of nutrients like oxygen. Picture a tumour spheroid as a clump of cells, growing in a sphere shape with a source of oxygen surrounding it. Oxygen diffuses through the ball, being consumed by the cells. However, at a certain size, all the oxygen is consumed before it reaches the centre most cells, and these cells, starved of oxygen, die out. This leaves a void of dead cells in the centre. The outermost well oxygenated cells are still happily eating oxygen and making clones of themselves, but the inner bunch die off, resulting is something like a hollow ball.

This pretty little thing is actually a stained cross-section of a DLD1 colorectal tumour spheroid - The centre is starved of oxygen or anoxic and the cells here die off. The cells in red are becoming hypoxic and the green ones are still merrily dividing.

In the paper just published, we derive a mathematical model which predicts oxygen level at any point in the spheroid, and explicitly predicts the boundaries of a tumour. This model can then be used to estimate the consumption rate of the tumour cells. Consumption rate is important, as cells which are oxygen hungry will devour diffusing oxygen quickly, resulting in more hypoxia and a thinner "shell" - in essence, consumption rate decides the extent of hypoxia to a large degree. 

Of course, theory is fun but it's important to validate it - we did that by using a series of DLD1 tumour spheroids, which fit the model very well and allowed us to pull out the estimated consumption rate. Spheroids are in some respects a very simple model of cancer as they're divorced from the complicated vasculature (blood supply) of a real human tumour, but the fundamental principle of oxygen diffusion and consumption is the same throughout, so understanding the relationships between consumption and oxygen status is a good first step. 
The whole thing is an interesting combination of physics, mathematics and biology. If you're interested in the detail, the paper is open access and available from Royal Society Interface here

2. Climate change denial and motivated reasoning
Back in October I wrote an unashamedly scathing rebuttal of climate-change denialism for the Irish Times, which is viewable here. The overwhelming scientific consensus is that climate change is real and that we've caused it, yet despite that there are a sizable bulk of politicians, media commenters and irksome people who try to maintain the utterly untenable position that climate change is a myth. Rather than repeat myself, I'll steal from the piece -

"..Such contrarian writers and broadcasters paint themselves as climate “sceptics”, but this is a calculated misnomer. Scepticism is an essential part of scientific endeavour. It demands all claims are treated as unproven until evidence and experience either confirm or falsify them. Denialism, by contrast, is the stubborn and persistent refusal to acknowledge what the evidence shows beyond all reasonable doubt. Evidence for climate change is overwhelming, confirmed by measurement, theory and experiment. Self-proclaimed climate “sceptics” are nothing of the sort; they are rank denialists, deliberately refusing to accept the incontrovertible evidence that their position is untenable."

As expected, the bog-standard climate trolls appeared in the comments and on my twitter feed within hours. Parroting the same pack of tired false buttals and quite literally calling black white; despite having an idealistic thing against blocking, the stream of aggressive nonsense ensured the block button on twitter became my friend. The demographics of the negative responses interested me though; they were all male, politically conservative with strong free-market views. Was there something to this?

Of course, anecdotal evidence is not evidence, so I had a peek at the literature to see if anyone had studied this from a psychological point of view and hey, presto - climate change denial  is associated with a particular set of conservative beliefs and a distaste for any form of regulation. But it isn't solely the preserve of conservatives to deny evidence to fit a pre-existing worldview; liberals can be just as guilty of dismissing solutions like nuclear power based on their own emotional reaction rather than the evidence. This is part of a phenomenon called motivated reasoning, where reality is filtered and selectively taken on board to pacify rather than challenge a preconceived notion.

Festinger explains motivated reasoning - I couldn't find one of that cliche quote things so I made one myself in ten seconds with that bastion of cutting edge photo manipulation Microsoft paint - because quotes with pictures is internet currency!

I penned a Guardian piece on this very subject, arguing that pragmatic decisions have to be made - decisions based not on some dubious worldview but grounded on the available evidence. Perhaps this is wishful thinking, but I am dearly hoping we can collectively get our act together as a species. Am I being too optimistic? Have a gander and tell me yourself!

3. On why our ideological fixations blind us to reality

On the subject of fooling ourselves, I did a little bit for the Irish Times on this very subject back in January, investigating our collective staggering ability to get everything wrong about everything and still think we're good judges of those very things. 

4. Homosexuality, nature and same sex marriage
As the same-sex marriage referendum in Ireland appears on the horizon, the usual suspects (whom we cannot mention because in a neat Orwellian trick,  pointing out people are being homophobic is apparently hate speech now - for context if you don't follow Irish Media see here!)  are out shrieking about how damaging all this is to the "sanctity" of marriage and OH GOOD LORD WON'T SOMEONE THINK OF THE CHILDREN?!

Helen Lovejoy - Iona material
Somewhere in all this sound and fury, the biological fact that homosexuality is perfectly natural has been glossed over by the anti-equality side, and the equally ominous insinuation that gay people are merely morally deviant scallywags who shouldn't raise kids is all too often made. I've poked that hornet's nest before over a certain institute's ramblings (Write up on that fun time here!) but decided it was important to yet again that homosexuality is perfectly normal and is not some strange lifestyle choice for deviants. I This ran in the Irish Times is December and you can take a peek hereEssentially , the take home message is

"Denying homosexuals the rights that are accorded to heterosexuals is not defending marriage or children, it is barefaced discrimination and no amount of oratorical dexterity or false expressions of concern can get over that."

On a side note I cannot help but feel I'd have more respect for that particular organisation if they just came out and said they had a religious ideological problem with homosexuality than their continued attempts to scaremonger the general public into supporting their dubious position. I'd still disagree to the hilt, but it would be far more honest than their current carry on. 

Warning: Some pretty homophobic comments under the tagline.

Right, that's your information overload for now. More focused post coming up soon!

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