Via an article I found this morning in the BBC I found about a recent piece of research about locust published in Current Biology abo .

Interestingly it seems that the reason that locusts combine into swarms is out of fear of being eaten by other locusts. Although locust are normally herbivore, when food becomes scarce some of them might resort to cannibalism.

And that is interesting in the sense that these highly aggressive (from the way they travel and eat) swarms are made of the less aggressive individuals that band together and escape from the cannibals, with devastating consequences. This is rather similar to what some researchers are finding in tumours, both experimentally and theoretically. As was discussed in previous posts (here or here for instance) reverting to a glycolytic metabolism allows tumour cells to survive in environments poor in oxygen while harming their neighbours. It has been hypothesised that motile tumour cells are more likely to appear if there is an increase in the acidity of the environment, in many cases as a consequence of the existence of these glycolytic cells (I should give a disclaimer and say that one of my papers is devoted to study this using game theory). Could it be a similar phenomena? that is, that less aggressive cell types escape from the more aggressive ones and that the consequence is also devastating (since these motile cells are responsible for the invasion and metastasis that characterise the last stages in cancer). Probably not very useful as an analogy: I am not sure how these researchers measured the fear of locust to their cannibal colleagues but it is safe to assume that tumour cells do not have much of that. Still fear is an instinct for self preservation that has a parallel in the microcosms of a tumour.

Browsing the New York Times online today I found this interesting article (and a related editorial).

Intelligence is one of these fuzzy concepts that are so difficult to define formally. We all have some intuitive idea of what it is to be intelligent and in most cases involves some capability to solve new problems and learn from past experiences. So, it is intelligence something unavoidable in evolutionary terms? and, as the article asks, if intelligence is something so great why is it that you don’t find it in most species?

It is important to make clear that most ‘complex’ species have some degree of intelligence and that even fruit flies are capable of learning. According to the article, most species with a nervous system (and some without them, just using their genetic network, and network is here the keyword) can behave non instinctively.

What is more interesting, it is possible to obtain smarter flies by selecting, in a lab, for those individuals that are more capable of learning. In only 15 generations the researchers found that the flies have evolved to learn faster. So why don’t you see smarter flies in the wild? When you mix these ‘smarter’ flies with the original kind they found that the smarter kind where less likely to survive. Actually when the ‘smart’ flies were places in a nutrient-poor environment and allowed to evolve the researchers found that after 30 generations the flies were less clever. It seems that brains come with a price tag and it might be that only very specific environments lead to a selective pressure that could make a complex neural system such as ours (that consumes 20% of all calories burned at rest) something worth investing in. It should be also an environment in which non specialised agents can buy enough time to learn and improve.

A relatively new issue of Science (4th of April this year) has an interesting editorial about the value of cancer research.

He claims that some people would like to see the money that is invested in the most fundamental of cancer research directly into the design of treatments and therapies. Something like we know enough about Cancer so let’s stop wasting time and money and let’s start doing things with what we already know. That is for me a rather surprising attitude: since I started working with cancer researchers what I found most surprising is not the amount of things we know, but the opposite, how little do we know after all the time and money invested in research. This is, of course, not the fault of cancer scientists but more the result of the extreme and incredible complexity of cancer as a disease. If there is something we need now is more fundamental research, and if you keep asking me, more theoretical research so we can knit all this knowledge into a cohesive set of laws.

Bruce Alberts, Science’s editor in chief describes examples of how a better understanding of the fundamental mechanisms could go a long way on improving cancer therapies. Specifically he mentions apoptosis and DNA repair which he identifies as two of the most promising areas of research with a potential impact in treating cancer.

The importance of the first one is not difficult to grasp. Cells in multi cellular organisms have a tendency to commit something akin to suicide and only constant reassurances from the environment that they are doing ok prevent them from doing so. Avoiding apoptosis is one of the most important milestones of a tumour cell, otherwise its chance of provoking havoc is somewhat limited.

The second mechanism is less straight forward in my opinion. A flawless DNA repair mechanism should prevent harmful mutations in the first place and will lead to apoptosis if the reparation is not doable. Thus a tumour cell should aim to have a less than perfect DNA repair mechanism in order to accumulate the necessary genetic mutations. For that exact same reason, a therapy that could re establish the functionality of the DNA repair mechanism would go a long way in making sure that abnormal cells die (due to apoptosis) whereas healthy cells stay.

These two are only a sample of things that the author argues we don’t know well and which deserve ample funding even when the hope of getting a therapy out of the money invested is not in the short term. I’d argue that I know a few more areas worth investing on but that might not be entirely unbiased…

Giving the finishing touches to a paper which I am writing with people in Dresden and Lyon, I came across an interesting article:

R. Gatenby and R. Gillies. A microenvironmental model of carcinogenesis. Nature Reviews Cancer 8, 56-61 (2008)

Neither Gatenby nor Gillies are mathematicians (the first is a physician whereas the second is a biologist) but both have worked before on some rather interesting models of carcinogenesis. In this paper they again introduced one of their models, constructed around a differential equation with a Lotka-Volterra term, in order to study how the microenvironment contributes to select phenotypical traits (conferred by genetic mutations).

• Insensitivity to anti growth signals.
• Self sufficiency in growth signals.
• Limitless replication.
• Abnormally high glucose uptake
• Resistance to acid mediated toxicity
• Invasion and metastases with sustained angiogenesis

This list is very similar to the one proposed by Hanahan and Weinberg (which long time readers of this blog might be familiar with). The biggest difference is the emphasis on acidity and glucose consumption, stuff related with the glycolytic metabolism, whose importance in tumour progression has been championed by Gatenby.

This is very relevant research and the authors do well to point out that most cell-centric models study tumour progression without questioning much why specific phenotypical changes are necessary. The answer is of course in the microenvironment, that allows those phenotypes that are better adapted to survive and grow. Microenvironental features represent barriers that limit tumour growth and thus, the phenotypes that manage to overcome them (whatever the genetic or epigenetic mechanism they exploit) will prosper, probably at the expense of the less adapted phenotypes.

As I am working on a project to study the role of TGF-Beta in prostate tumour progression (see more on an older post), everything TGF-Beta related catches my attention.

The Transforming Growth Factor Beta (or just TGFB) are a family of proteins that control cell proliferation and differentiation. I hope that my friends at Vanderbilt will correct me if they don’t agree with the statement that an imbalance in TGFB production and consumption could lead to uncontrolled growth and potentially to the beginning of a tumour.

Now, a group of researchers from New York and Barcelona led by Joan Massague have shown how TGFB plays also an important role by improving the chances of tumour cells originated in the breast to better to metastasise in the lung (although, curiously not in the bone). The research is reported in this week’s issue of Cell (as well as in the Spanish press for those of you that speak Spanish).

The research shows that TGFB allows cells to depart the primary tumour and empowers to disrupt the walls of capillaries in the lung vastly improving their chances of establishing a new tumour colony.

Since the last topic about drinks was so popular among some of my friends (which makes most of the readership of this blog anyway), now I continue with something I read today at the BBC’s website. Researchers at the University of North Dakota have found that caffeine can act as a blood flood barrier and thus protect the brain from some of the harmful elements that are present in the bloodstream (not all of it made of oxygen, immune cells and other desirable things). The research, tested on rabbits and published at the Journal of Neuroinflammation, suggests that one cup of coffee a day (or its equivalent in terms of caffeine) might help to prevent Alzheimer. And if it is good enough for a rabbit, then it is good enough for me!

Now, if you excuse me, I am off to get an espresso.

UPDATE: Seems that neither beer nor water are that good for you. I am off for another ristretto.

Bad news for those of us that believe that a pint (some might say that a pint is only a promising start) after a long day’s work is only a nice way to chill out and recharge batteries for the next day (of more hard work?). According to a study published in Oikos , consumption of beer correlates with scientific productivity ... and not in the way that some of us would hope for. Moreover, the study comes from Czech scientists. The Czech republic is said to have the highest per capita consumption of beer in the world. So if Czech researchers say that beer is not good for scientists, they certainly have written this with a heavy heart.

Basically the research shows that publication success is correlated, in the fields of behavioural and evolutionary ecology in the Czech republic, and that this correlation happens even when the subject of research drank only a glass (and more so when they drink more than that). This correlation is negative so the more they drink the poorer the publication record.

I found this research mentioned in the NYT and one of the comments was (not entirely unexpected) that correlation is not causation and that beer drinking might not be responsible for poor academic success but probably the other way round: poor academic success leads researchers to drink more. I for one keep my fingers crossed that these people don’t start studying now the influence of red wine. Some times ignorance is bliss…

UPDATE: Apparently (and unsurprisingly) not everybody agrees with the methodology and conclusions of this paper.

Two articles from a recent issue of nature ([here and [here]) raise the issue of how genetic diversity may affect anti-tumour chemotherapies. A nice overview of the significance of these articles in the grander scale is also provided [here].

The two papers mention research that could be included in the nascent field of pharmacogenomics in which scientists study how genetic variation (like the one found in a typical tumour) affects the response to a drug in terms of efficacy or toxicity. And of course it seems that this diversity has a huge and rather negative impact on the efficacy of the drugs. When a particular cancer gene can have its effect duplicated by a mutation in a different gene then a therapy that targets cells with the first type of mutation are effectively selecting for cells with the second kind. This is not necessarily a bad thing but at least should be taken on account before pursuing any option. If selecting for a tumour composed by this second alternative mutation leads to a tumour that is effectively easier to treat then the treatment is a good one. But it could also happen that things go the other way and a drug helps the tumour evolve towards malignancy.

One way to stop tumour (somatic) evolution is to target more than one mutant simultaneously, although this also makes it more likely that there will be side effects that will be felt by healthy cells. A different approach has been announced recently. This approach fights evolution with evolution with a virus that helps to fight brain tumour cells. This is an exciting development that is being currently used by researchers in Yale to treat very serious cases in a type of tumour, brain tumours, in which tumour growth happens very rapidly and in which surgery is very complicated. In any case one is left wondering what will stop the virus to evolve to attach healthier cells once the tumour cells it lived on start being scarce.

I do follow some scienceblogs out there. The New York Times hosts one from Olivia Judson called The Wild Side about evolutionary biology. The blog is very well written, which is not surprise coming from a professional writer (and research fellow at Imperial College London). The entry a few days ago was about the role of mistakes in evolution. The mistakes she was writing about are the mutations that occur duplicating the genetic material during cell division.

What she argues is that mutations are not necessarily an imperfection of our reproductive system but, especially in asexual species, the means for adaptation. The claim gets more interesting because, if a given rate of mutations is something that allows adaptation, then the mutation rate itself could be subject to adaptation. Turns out that this is true. As I had read before somewhere else and as I blogged about before when talking about the mutator phenotype hypothesis, the mutation rate adapts itself in order to suit the particular environment in which the evolving system lives (I’d rather call it evolving system since RNA viruses are not normally considered living beings). Thus in difficult environments it pays off to have a higher rate of mutation so that a viable phenotype will be found quickly even at the cost of having to produce plenty of absolutely inviable phenotypes at the same time. In nicer environments where many alternative phenotypes can survive then, a high mutation rate is more likely to be counter productive.

These facts should be applicable to cancer. The rate of mutation can be altered by changes in the DNA repair machinery and the various checkpoints in the cell cycle. Some cells with perfectly functioning DNA repair mechanisms are unlikely to divide producing mutations along the way. Others with mutations in, say, p53, are more likely to make mistakes during mitosis. As a consequence, someone correct me if I am wrong here, it should be reasonable to expect that tumour cells in those parts of a tumour that inhabit harsh micro-environments, should have a higher rate of mutation. This higher rate of mutation should be the result not only of the fact that tumour cells keep accumulating genetic aberrations but more importantly, from the fact that those cells in harsh environments that insist in keeping a well oiled and preserved division mechanism will be less likely to adapt and survive. Seems like an interesting problem that could be formulated in terms of mathematical biology.

As a Spaniard doing research abroad I feel I should have an opinion of the state of Spanish science. On the other hand I feel I have a more solid experience of the state of Science in places like the UK or Germany than in my own country.

For that reason I am always happy to read and listen to people and publications that discuss the potential of Spanish research in relation to that of the leading Scientific countries of the world. One of the things that, in my opinion, is easier to have when you see things from afar is a slightly more impartial view. According to reports like this a few years ago in Nature and authored by David King (then the chief advisor to the British government in scientific issues) Spain is far from being the worst place in the world to do science but neither is close enough to be an ideal destination. Good science is possible if you work hard and refuse to submit to burocracy and all the organisational mechanisms designed to keep in the conformists and out the rest. I know some Spanish scientists and I know that it is possible to produce good research but I also suspect that any of them would have had a much easier life if they had decided to move to a different place.

The editorial in this week’s Nature on occasion of the coming general elections seems to point in that direction too. It mentions the efforts of the current administration significantly increasing the proportion of the GDP invested in Science which now has reached the level of 1.1% (which is clearly well bellow the quantity and quality invested by many EU countries, let alone Japan or the US). It also mentions what remains to be done which is to restructure the R&D of Spain and especially the main research council, the CSIC, so as to make sure that the new money that has arrived (and that should keep arriving) will reward the best scientific projects and the best researchers.

It is quite remarkable that the article keeps referring to a future silver age: as opposed to the cultural front, Spain has never been part of the scientific elite. In any case, with all this time smelling bronze, silver should be a welcomed change.