Tridimity

Tumour cells tend to shut down mitochondria, the sites of oxidative phosphorylation and the intrinsic pathway of apoptosis. The former is beneficial for the transformed cell because, typically, the cells in the interior of a tumour will be experiencing conditions of hypoxia (even if the tumour cells have induced an angiogenic response, the resulting blood-vessels tend to be rudimentary, leaky and disorganised with many dead-ends) and so it is preferable for them to rely on Oxygen*-independent substrate level glycolysis as a means of generating ATP (even if the energy yield is less than the output of the citric acid cycle and oxidative phosphorylation). The pyruvate generated from glycolysis is often shunted into the lactate dehydrogenase-catalysed production of lactate, rather than into the pyruvate dehydrogenase-catalysed production of acetyl CoA for entry into the citric acid cycle. The lactate is then extruded by transformed cells to be taken up and used by respiring stromal or tumour cells, thereby saving glucose for use by hypoxic tumour cells. The latter is, of course, beneficial as it allows tumour cells to survive even in the presence of signals that would ordinarily seal their demise. It has also been suggested that the use of a ketogenic (low carbohydrate, high fat - medium chain triglyceride) diet may be beneficial for cancer patients, since the diet relies on the consumption of food that does not increase plasma glucose levels, but produces ketone bodies (D-3-hydroxybutyrate, acetoacetate and acetone) that can be used as a Carbon* source for energy production. These bypass glycolysis and are metabolised by mitochondria in the presence of Oxygen*. Normal cells can adapt to using ketone bodies to produce ATP but tumour cells rely on high glycolytic flux and so would not be expected to survive on this alternative fuel source. Some in vivo and clinical studies have reported decreased tumour growth - even in cachexic patients, however a different study has reported negative results. *Out of a mark of respect for the chemical elements, I like to capitalise the first letter of their names, have done so since I was 11 and not about to stop now. I hope that this is not too disconcerting for readers.

Like telomere lengthening? I agree that traditional treatments for cancer (surgery, radiation therapy and classic chemotherapies) are too crude, ineffective and pose too many long- and short- term side effects including, in some cases, infertility. For these reasons we urgently require more rationally-designed drugs - selective inhibitors of oncoproteins and agents that promote tumour suppressor function - for the treatment of different cancer types. Some of these are finally trickling down from big pharma but, even so, on the whole they only extend lifespan by a few months to a couple of years at most. Whether or not they improve quality of life during this time is questionable. Such agents need to be used in combination on the basis of the unique genetic and proteomic profile of the individual patient's cancer (personalised medicine). I would argue that even this is not quite enough and that what will ultimately help to defeat cancer to the point of reliable functional cure, is to generate molecular profiles of cells from many different parts of the tumour or metastases and from the surrounding tissues - on a single-cell basis - so that the variability between individual cells in a tumour is not ignored. It is not acceptable to perform a Western on tissue derived from one area of the tumour and to claim that the observed protein levels are representative of each of the individual cells within the tumour. Since tumours develop as a series of clonal expansions, to ignore the details of between-cell variability is to grant the minority of cells that have the biological capacity to resist any rationally-designed monotherapy, the chance to do so and to permit relapse. Improved management of the care of cancer patients is, of course, always desirable. How would this be achieved, where is there room for improvement? Any physician worth her or his salt will already present patients with the array of options that they have in deciding on an appropriate cancer treatment regimen. This will depend very much so on the priorities of the patient: are they willing to tolerate the side-effects of treatment for the sake of an additional year's survival? Perhaps there is some very special event that is of great personal importance to them and which they wish to attend before they die - the birth of a family member, a marriage - or maybe they just want to see the sun rise in its chariot of gold 365 more dawns? For others, the side-effects of treatment may be deemed too physically challenging for the patient and too psychologically and emotionally distressing for the patient and their loved ones. One area of management that, I think, could certainly use immediate improvement is the provision of effective counselling services for the patient and their family and friends. Earlier detection would also help in identifying tumours before they have become invasive and metastatic - and before they have become more resistant to currently available chemotherapies.

Did you do the abdominal vibration? Awesome video EdEarl!

I appreciate that, on the whole, a universal cure for cancer would not actually extend the average lifespan by very much - precisely because age is a risk factor for the development of cancer. Acquiring the suite of mutations and number of cell doublings implicated in cancer - not to mention the development of anti-apoptotic, invasive and metastatic phenotypes in cancer cells - takes decades usually. But to claim that, 'in the aggregate, it's not as big an advance as you might think.' Really? Is this guy in his right mind? I can only assume that he has never witnessed the protracted death of a loved one to this disease; has never witnessed their intense physical discomfort and pain and the psychological and emotional impact on both the patient and their family and friends. It's not all about how long you ward off death - it's also about the way in which you die.

So, I was thinking recently about the ethics of the principle of so-called designer babies. I know there have been a few (three, to be precise) previous threads on the topic, but they are all a few years old now, and tended to focus a lot on whether or not the deliberate genetic modification of gametes and/or embryos to create human offspring with certain specifications is biologically plausible. An equally interesting question concerns whether or not it is ethical to create designer babies? In order to be considered ethical, the practice must fulfill the following criteria: No living humans should be harmed (physically, psychologically or emotionally) by the implications of the procedure The offspring should not be harmed (physically, psychologically or emotionally) by the implications of the procedure Some may consider that, in creating a designer baby, one is effectively choosing not to have a baby that would otherwise have been conceived naturally - and so, it is argued, the interests of these potential or would-have-been offspring ought to be considered. Presumably these people genuflect before their own gametes. These criteria may sound simple, but complications arise when attempting to define and predict 'harm'. As for the second point, it would seem that the designer offspring have little to lose from the concept and much to gain. There is, of course, the possibility of side-effects of the necessary procedures - but this is true of any medical intervention and so does not constitute grounds for immediate dismissal of the proposal. A member previously mentioned that it is impossible to predict the future environmental conditions under which the offspring will be living and so, likewise, it is impossible to design the genetics of the offspring in such a way that it is best suited to its environment. Still, the same is true for standard, naturally-derived genomes: such genomes have been shaped through the process of natural selection to best suit the environment in which the organism's ancestors lived. This provides no guarantees for a future with uncertain environmental challenges on the horizon. The latter point does, however, inspire an appreciation for the efficacy of natural selection in shaping genotype and phenotype so as to produce organisms that are very good indeed at acting as gene propagators. Blind though the process is, perhaps we ought not to tamper with Evolution? One counter point that I would make, is that the timescales involved would allow for rapid modification of the genetic make-up of the next generation. Still, the procedure would constitute a major social experiment. The first point, above, possibly holds the key to the visceral resistance to the concept of creating designer babies. Since we are the products of Evolution, is it not likely that we would defend the very process that has created us? The biological desire to propagate our genes drives Evolution; it is natural that we should wish our own personal genome to be merged with that of the fittest possible person of the opposite sex. Genetic manipulation would render the latter point moot - we would no longer need to expend so much time and energy in searching out the ideal mate (what would happen to our culture? No rom-coms?) but we would probably still wish for our own genes, however imperfect, to be loaded alongside those that we have specified as desirable. Isn't that a little selfish? Doesn't it prove that actually our interests are nothing more than self-interest - we do not have the offspring's best interest at heart (if we did, then presumably we would wish for them to be as fit, in evolutionary terms, as possible - which may well mean contributing specially selected genes, none of which are our own?). The point is - perhaps living humans would be 'harmed' (or at least, would not get their own way) where designer babies are concerned, since it could mean sacrificing their opportunity to pass their own fallible genes into the next generation (contrast this with the case of eugenics in which there is obvious suffering caused to living humans). Hypothesis: the visceral reaction to designer babies stems from a reluctance to move to a situation in which the 'perfecting' of the genomes of offspring means sacrificing the interest of the parent?

Naughty Boy La La La ft. Sam Smith http://www.youtube.com/watch?v=3O1_3zBUKM8

Why might laughter have evolved as a response to mild breach of social conventions? Might laughter act as a social cohesive, a means for human groups to define rules?

Benign temporary suspension of expected social mores But - why does that result in the psychological response and the physical act of laughter?

What is it about the concept that you deem outlandish? Nobody is suggesting that there was a formal round table discussion, or that the convention was borne of an exclusively American demographic. The terminology used will reflect the societal values and prejudices prevalent at the time of their invention - in this case, genophobia. Religious institutions tend to promote genophobic attitudes and have been known to do so historically - at a time when sexual swear words were being conceived (take or leave the pun). The religious right is still highly influential in the US. As such, Phi's hypothesis is reasonable. Villain - please read Phi's point above. The suggestion is not that religious institutions conspired to create a dictionary of insults based on sexual references. Nothing exists in isolation; the psychology of the religious individuals will have been a contributing factor - but because historically almost everyone was religious (indeed, it was typically lethal to be otherwise). For example, the term 'slut', as we understand it today, originated in the 15th century, a time of high religiosity: Correlation does not necessarily equate to causation - but certainty about causation is not a pre-requisite for a reasonable hypothesis (indeed, there would be no point in the hypothesis if it were). The language associated with insults has not caught up with the sexual revolution.

Science Britannica, Professor Brian Cox, BBC2, starting 18th September, watch it! http://www.bbc.co.uk/mediacentre/mediapacks/geniusofinvention/celebrating-invention.html

Thanks Iota, you are probably right in that honesty is preferable. I wish I had not been caught off guard when my nephew asked, I wish I had been proactive in thinking about the optimal response to the inevitable question before it was raised. Hey-ho! Now to prepare for the next questions, 'why did you lie to me?' and, 'why would my goldfish want to watch over me?' (It probably only irritates him to see another fish eating his food...)

Recently, when looking after my niece and nephew, I had to broach the subject of death. The death of a previous pet goldfish was mentioned and my nephew asked, 'Is he in Heaven now?' Looking into his hopeful eyes, I found myself saying, 'Yes, he is, maybe he is even watching down from Heaven now' - despite the fact that there is no evidence for the existence of Heaven and I suspect the likelihood of its existence to be exceedingly close to zero. Of course, the reason I lied was to provide psychological and emotional comfort, but the question remains - is it morally justifiable to lie to a child in this way and to suppress their critical thinking skills? Is this not the recipe for a subsequent generation of adults who prefer to accept received 'wisdom' from authority figures, if and when that information is more emotionally appealing than the oftentimes difficult truth? By supporting religiosity in children, will the result be a generation of adults who are not prepared to question the nature of morality independently, but who accept moral atrocities including war, homophobia, sexism, child abuse and the sidelining of reasoned argument in favour of the religious 'ideal'?

Exactly Agreed, the side-effect is to demonise the act of sexual intercourse. Why can people not just accept the fact it happens and is natural and necessary? Perhaps it is a religious hangover here in the UK and in the US. Perhaps if we stop indoctrinating subsequent generations of children and stifling their curiosity on this matter then the subject would no longer be taboo; the cycle of unwarranted societal-induced shame could be broken once and for all. According to one study, ~90% of people reported that they have masturbated. So unless the insulter is one of the 1-in-10 who abstain, then frankly they are a hypocrite. In a world of finite resources and increasing population levels, the individual who uses this as an outlet may be more responsible than the person who brings into the world more offspring than can be maintained by them as parents, or by the world at large. Yes, there is probably a degree of religious hangover going on. True. In order to liberate the terms from their negative connotations, perhaps the anatomical labels should not be out-of-bounds. Then perhaps insults could become more intelligent; people could say what they mean rather than hiding behind a non-communicative blanket insult. Maybe insults could evolve to become neutral instruments for feedback on behaviour.

This ought not to warrant the status of 'topic' since it is a mere observational bugbear of mine. Has anyone else noticed that most of the obscene terms intended as insults do not actually make much sense as derogatory terms? This is especially true when the labels of genitalia are hijacked as slang terms and directed as an insult. In any other context, the reference to a functional part of the reproductive anatomy essential for perpetuation of the species - even in relation to oneself - would not be considered offensive. Probably the reason that people feel offense is because of the implicit intention of the insulter - to hurt the feelings of the insulted - and because of the unspoken consensus regarding the meaning of the term. For example, the term may mean, 'one who acts without restraint and pursues only self-interest; inconsiderate'. So why not just call somebody 'inconsiderate' instead of hijacking terminology reserved for functional anatomy?

Just the mental image of a stork, perched on one leg in a cell, incredulous and being stared out by paranoid authorities. Okay, I know it probably doesn't go down quite like that.

http://www.bbc.co.uk/news/blogs-magazine-monitor-23962379 From the BBC News Magazine Monitor:

It's an interesting question, WWLabRat. At what point does river X stop being river X? Water molecules are constantly flowing and so the description of the river at time point A, in terms of the precise arrangement of water molecules and other matter comprising the river, will be considerably different to the arrangement of molecules at time point B - even between time points separated by mere fractions of a second. By convention, the body of water would continue to be referred to as 'river X' until a noticeably drastic change occurred (e.g. drying up completely). Probably the limits of identification are determined to some extent by matters of scale: a few water molecules, here and there, relative to the size of the body of water and to the size of the observing human, is not such a big deal. Perhaps if we were to observe things from the perspective of a bacterium, each individual water molecule would suddenly have more importance in determining the identity of the body of water? As for human identity - our cells die and are replaced throughout life but our individual genome sequence passes, consistently (except for mutations and epigenetic effects) down the cell generations. As such, the genome sequence confers a unique identity upon each individual. Also, perhaps the time frame of observation is an important contributing factor when defining identity. Perhaps we should define people and objects according to their entire lifespan or existence, rather than as a static object at one point in time. The former is counter-intuitive because, in general, in life, we need to be able to identify people and objects on the basis of how we find them at a particular time point - and so we have become accustomed to so doing. However, the question is, where to draw the line? Is a person defined at the baby up to the deceased? Should the foetus be involved in the identification of the person? Should the gametes? By extension, should the parents and offspring; the ancestors way back to the universal ancestor? Should all of the descendants be included? Nothing exists in isolation, and so, in a sense, we all share identity.

. Well, yes, a combination of reference and science non-fiction (so-called 'smart thinking') books would be preferable. Still, there has to come a point at which children, if they wish to pursue Science, are brought up to speed on scientific theories and conventions - even those as straightforward as SI units - fact finders are ideal for this purpose. Children are naturally inquisitive and so if you wish them to learn to ask the right kinds of questions about the natural world, and to begin to address those questions using a scientific approach, supervising their hands-on experiments would be very helpful. Depends on the interests of the children - in this case, according to the OP, the children are interested in diseases.

We do not yet know what preceded the Big Bang. This does not equate to the beginning of the Universe being ‘supernatural’. An event that has occurred in reality, and that would be observable were it not for the lack of technical ability to observe the event, does not a supernatural event make. It is not acceptable to hijack areas of knowledge in which - so far, at least - Science is ignorant and to claim those areas as being of a religious/spiritual nature. Individuals are, of course, free to subscribe to religious doctrine where such matters are concerned, but I do not see how such a choice is useful in promoting the advancement of knowledge regarding the natural world. In fact, I would imagine that the religious position, when used in this way, does more to hold back the progression of knowledge about the natural world. The only advantage of adhering to the religious viewpoint on such as-yet uncharted territories, is to deliver a degree of psychological comfort. Even so, the comfort is of the wishful-thinking kind, and in my opinion is less potent than that comfort provided by knowing with certainty the truth accessible by way of observation and reasoned argument. The fact is that some people ascribe the order observable in nature to the workings of an omnipotent being whom defies the Laws of nature, hence, ‘Goddidit’. We are all equally able to access the natural evidence that surrounds us every day. What I fail to understand, is why some people choose to take this evidence as proof of the existence of a deity, whereas others interpret the evidence for what it is - information about the natural world – and accept the temporary barriers to our knowledge represented by technological deficiencies, without enlisting the doctrine of a Creator. Such theists study the natural world using a scientific approach and yet somehow fail to extend the scientific approach when it comes to areas about which Science is temporarily silent (such as the beginning of the Universe); instead, they advocate the concept of a Creator – flying in the face of Occam’s razor. Why? Why do they believe that there needs to be a reason for existence? The fact that the Truth is interpreted by some as being offensive does not make it less true. Should we shield the over-sensitive types from the fact that the sky is blue? Correct, this is how Philosophy has advanced historically. However, just because the path to enlightenment in the past involved a stepwise progression from observation through to questioning and superstition, then on to more questioning and finally to a scientific approach, does not mean to say that we must dogmatically follow all of the steps in the routine in order to understand the natural world. To do so would make us no less stupid than Skinner’s superstitious pigeons, performing arbitrary routines in the hope of securing knowledge, due to a learned association between superstition and ultimate knowledge. While our previous superstitious approaches are interesting from a historical perspective, they have been superseded by the scientific approach – to revert would be to needlessly stall our intellectual advancement. As previously stated, just because there are natural phenomena about which contemporary Science is ignorant does not mean to say that that will always be the case. Science is an ongoing human endeavour to understand the Universe – which does not happen overnight! In the meantime, it is not helpful to attempt to plug the uncharted territory with religious superstitions, anymore than it was helpful to ascribe the aetiology of various (bacterial and viral) pathologies to ‘evil spirits’ in times pre-dating microscopy.

I can understand your not wanting to see her with a new partner and for this reason it is probably wise to have constructed definite boundaries. For the sake of your own interests in, say, five or ten years time - when you will probably have moved on and be happy with a new partner, and when you no longer have any wish to return to your ex-wife - it might be worth keeping a channel of communication that you can use in the future. You may find that you miss her as a friend and miss her company. I suppose that's one of the hardest things about divorce: you wish to seek comfort from your best friend, only, your best friend is now your ex. She has had a very substantial impact on your life - and you on hers - and no amount of time will erase that. For this reason, it may be worth keeping contact avenues open, even if at times it does feel like the Moscow-Washington hotline

Recently read Danny Dorling's '10 Billion', in which he essentially argues that - contrary to the scaremongering of apocalyptist types - global human population will probably peak at (at most) 10 billion by 2100. Fertility rates in most Western countries have actually been falling in the past couple of decades, although there are blips such as the current bucking of the trend in the UK, which is thought to be due to the latency associated with mothers giving birth on average at a later stage in life when compared with previous generations - while longevity is increasing. He also argues that, rather than worrying too much about population levels per se, what is really critical to survival of our species (and that of others) is the way in which we all live. A world in which there are 10 billion people engaging in environmentally-friendly lifestyles may well be more sustainable than a world in which there are 7 billion people engaging in wasteful lifestyles that fuel climate change. The problem is not that Earth lacks sufficient resources to sustain 10 billion people - rather, the problem is that the available resources are not being distributed in an intelligent fashion. As such, the highest birth rates continue to be found in those less economically developed countries (LEDCs) which experience high infant mortality. The association between economically-related infant mortality rates and birth rates is exemplified by women who migrate from LEDCs to MEDCs and adopt the birth rate of the new country. We can therefore reasonably expect that a fairer global distribution of resources would be paralleled with a commensurate stabilisation of population levels. No longer can we treat socioeconomics and climate change as two independent variables. What we need is a smart world - a world of people connected by their fundamental humanity - with sophisticated communication systems, in which countries maintain their national identity without forsaking the greater picture.

Hey swansont, I have been reading your Swans on Tea blog, I don't understand the Physics (no surprise there) but your posts are very witty. You have a great sense of humour and I enjoy reading them, so thanks Trying to reach 50 posts so that I can start a Biology blog. Best wishes, Tri

I don't know the details of the nature of the separation between you and your wife, but it seems a shame that you should lose your extended family as a result of private matters between the two of you. Is there no scope for you to be able to stay on amicable terms with your ex-wife? Couldn't you meet occasionally as friends? Perhaps it is too soon for that and you both need time to emotionally process the ramifications of your divorce. But perhaps you could get to that place of neutrality and friendship? Likewise, would it be possible for you to maintain your relationships with members of her family (or do you no longer wish to do this)? Whatever happens, it would be good for you to strengthen and widen your circle of friends. Also, depending on the severity of your sadness, you may wish to seek the help of a counsellor. Best wishes, Tri

We are all animals, yourself included. You don’t get to have an opinion where facts are concerned. We have evolved the co-operative traits necessary to survive in social groups. It is possible to live in complete isolation from the rest of humanity, if one so wishes, but I do not think that this would be an easy or enjoyable life, on the whole. As such, rules are a necessary part of social life. Problems arise when the rules are not conducive to the wellbeing of certain individuals or groups – but that is why we have the field of Politics.

Hm, how about a Science encyclopedia? Also a Science 'fact-finder' - to introduce scientific concepts (and constants) concisely. The advantage with these types of reference books is that they explain each concept with clarity and in sufficient depth while also allowing for great breadth. They also tend to focus on the essential and timeless key points of Science, that will always be useful to know. E.g. Chambers Science Fact Finder http://www.amazon.co.uk/Chambers-Science-Factfinder-Factfinders-ed/dp/0550101489