Many ecologists study evolution of the non somatic kind. That is, evolution that happens as a consequence of mutations in the germ line of multicellular organisms during reproduction. The evolution of cancer is of the somatic kind. This means that it affects cells of the soma, the ones that are not transmitted to the offspring.
Some time ago I got this paper from Crespi and Summers (nicely enough, publicly available). I will probably talk about this paper, entitled Evolutionary biology of cancer (and presented to a readership of ecologists) some other time but I liked a table in which they compare somatic and non somatic evolution.
Phenotypic variation. In most ecosystems of multicellular organisms variation is attained through genetic recombination (sexual reproduction) and mutation. In a tumour we also have to consider also genomic instability (a hypothesis by which some individuals have a higher probability of mutation) and epigenetic alteration (the environment also affects the behaviour of cells in ways that could make tumour progression to cancer more or less likely).
Selection. In most ecosystems it means dealing better with competitors, avoiding predators, parasites and producing many fit successors. In a tumour means being good at competing for resources with other cells (tumour or otherwise), avoiding the immune system and coping with environmental signals designed to maintain homeostasis.
Drift. That is similar in both types of evolution.
Inheritance. In many cases that involves the transmission of genes from parents to offspring through sexual recombination. In tumours there is no sexual reproduction.
Result. In most ecosystems the result is adaptation across generations. In a tumour the end results is in many cases the death of the individual and thus of all the cells in the body, including the cancer cells.
I think that this is a quite interesting and useful comparison of evolution although I am not sure I agree with all the differences suggested. In my view the evolution in a tumour does not differ much from other types of evolution. For instance, epigenetic changes do play a role in other ecosystems asides from cancer. Genetic instability is not a source of variation, genetic mutations are (genetic instability just makes genetic mutations more likely). Also the fact that tumour cells reproduce asexually is not a big difference with more conventional ecosystems. At the end of the day most of the biomass of the planet is made of bacteria that reproduces asexually. What it is true is that as far as we know, the end result of cancer evolution is either the end of the cancer itself or the end of the individual that hosts the cancer and thus the end of the cancer cells. Thus the only way tumour cells have to be successful is to evolve in such a way that the life of the host is not threatened (you can call that tumour sustainable growth).
Showing posts with label evolution. Show all posts
Showing posts with label evolution. Show all posts
Monday, May 14, 2007
Monday, May 07, 2007
Evolution and medicine
Catriona MacCallum, an editor at PLoS Biology has posted the following essay (being PLoS, it is available to everybody) about medicine and evolution.
According to the article, physicians do not get much of a training in evolution as a method to study the origin of diseases. That is because most of the training of physicists is not to make them good scientists but to make them good at treating patients. Quoting the article: "does a mechanic need to understand the origins, history and technological advances that have gone into the modern motor vehicle in order to fix it?".
This approach is not entirely wrong and once can treat things that are the result of an evolutionary process without having to spend too much time studying evolution. A different thing is when the disease is not a result of evolution but they are evolution itself. They never mention cancer in the article but cancer and infectious diseases are clear cases of diseases in which evolution should be dealt with if the disease is to be cured or even contained. Without an understanding of evolution a physician will be unable to understand how the bacteria or cancer cells will react and evolve when a treatment is used or what phenotypical traits are more likely to be evolved and thus cause problems to or be exploited by the medical community.
According to the article, physicians do not get much of a training in evolution as a method to study the origin of diseases. That is because most of the training of physicists is not to make them good scientists but to make them good at treating patients. Quoting the article: "does a mechanic need to understand the origins, history and technological advances that have gone into the modern motor vehicle in order to fix it?".
This approach is not entirely wrong and once can treat things that are the result of an evolutionary process without having to spend too much time studying evolution. A different thing is when the disease is not a result of evolution but they are evolution itself. They never mention cancer in the article but cancer and infectious diseases are clear cases of diseases in which evolution should be dealt with if the disease is to be cured or even contained. Without an understanding of evolution a physician will be unable to understand how the bacteria or cancer cells will react and evolve when a treatment is used or what phenotypical traits are more likely to be evolved and thus cause problems to or be exploited by the medical community.
Friday, April 27, 2007
evolution of multicellularity
A friend of mine has found this interesting essay in Nature entitled "Unity from conflict" that deals with the evolutionary mechanisms that allowed the emergence of multicellular organisms.
The problem of how multicellular organisms came about from single cells is quite intriguing. I heard from Lewis Wolpert that this is probably the most important of the seven transitions in evolution as described by Maynard Smith and Szathmáry in their book. In retrospect it is clear that such a transition is possible (since we are here) but, why did it happen?
Paul Rainey (whom I suspect might be a microbiologist) seems to be suggesting that with the right mutation rate (or right mutation bias) multi-cellularity should be possible. Organisms such as myxobacteria seem to be able to alter their mutation rate in response to stress in the environment so I guess that evolution fiddling with the right mutation rate is not unreasonable. In any case I'd rather see it from the point of view of my friend, that is, a harsh environment does enforce cooperation in a way that makes cheating very costly. In reality I would imagine that other factors such as the immune system (that in a way can be though of a police on the lookout for cheaters) or the fact that cells in a multicellular organism share the same DNA could also help explain why there is not that much cheating in our bodies.
This article is quite interesting for any one interested in cancer. At the end of the day a cancer cell is a normal cell that due to genetic or epigenetic reasons stops cooperating. Once they evolve the means to avoid the immune system and other mechanisms designed to maintain homeostasis I would imagine that the life expectancy of a tumour cell should be rather short (necrosis, running behind in the evolution game or due to a poor microenvironment) and thus crime might not pay, at least in the mid/long term (which still would leave room for a benefit in the short term that would be enough to kick-start somatic evolution).
It should be possible using a computational model to demonstrate that an aggressive microenvironment would favour cell cooperation. A mutlicellular organism in which individual cells suffer when exposed to the exterior would evolve a morphology that would minimise the interface with the outside world. it would be also quite likely that a niche of stem cells would evolve to be in charge of generating the cells in this interface that would be in need of constant repair and maintenance. That is what happens in places in which the environment is hostile to cells like the colon or the skin. If cells in the model are allowed to cheat (by means of mutations leading cells to try to avoid being part of the interface if that is their role) that would presumably affect negatively the overall fitness of the organism. However I am not sure that this would rule out other explanations for the evolution of multicellular organisms.
The problem of how multicellular organisms came about from single cells is quite intriguing. I heard from Lewis Wolpert that this is probably the most important of the seven transitions in evolution as described by Maynard Smith and Szathmáry in their book. In retrospect it is clear that such a transition is possible (since we are here) but, why did it happen?
Paul Rainey (whom I suspect might be a microbiologist) seems to be suggesting that with the right mutation rate (or right mutation bias) multi-cellularity should be possible. Organisms such as myxobacteria seem to be able to alter their mutation rate in response to stress in the environment so I guess that evolution fiddling with the right mutation rate is not unreasonable. In any case I'd rather see it from the point of view of my friend, that is, a harsh environment does enforce cooperation in a way that makes cheating very costly. In reality I would imagine that other factors such as the immune system (that in a way can be though of a police on the lookout for cheaters) or the fact that cells in a multicellular organism share the same DNA could also help explain why there is not that much cheating in our bodies.
This article is quite interesting for any one interested in cancer. At the end of the day a cancer cell is a normal cell that due to genetic or epigenetic reasons stops cooperating. Once they evolve the means to avoid the immune system and other mechanisms designed to maintain homeostasis I would imagine that the life expectancy of a tumour cell should be rather short (necrosis, running behind in the evolution game or due to a poor microenvironment) and thus crime might not pay, at least in the mid/long term (which still would leave room for a benefit in the short term that would be enough to kick-start somatic evolution).
It should be possible using a computational model to demonstrate that an aggressive microenvironment would favour cell cooperation. A mutlicellular organism in which individual cells suffer when exposed to the exterior would evolve a morphology that would minimise the interface with the outside world. it would be also quite likely that a niche of stem cells would evolve to be in charge of generating the cells in this interface that would be in need of constant repair and maintenance. That is what happens in places in which the environment is hostile to cells like the colon or the skin. If cells in the model are allowed to cheat (by means of mutations leading cells to try to avoid being part of the interface if that is their role) that would presumably affect negatively the overall fitness of the organism. However I am not sure that this would rule out other explanations for the evolution of multicellular organisms.
Monday, April 23, 2007
Acceptance of evolution around the world
National Geographic has published this chart that depicts the public acceptance of Darwinian evolution in 34 countries around the world. As a Spaniard I am happy to see that evolution is widely accepted in my country, with a higher acceptance rate than even in Germany where I currently live although not as high as in Scandinavian countries or in the UK (the birthplace of Darwin). In the U.S. less than half of the population (if the results of the poll can be extrapolated) have at least some reservations towards evolution although the country (of all those polled) that seems most hostile to it seems to be Turkey.
Tuesday, February 13, 2007
Lenski et al: Balancing robustness and evolvability
R. Lensi, J. Barrick and C. Ofria. Balancing robustness and evolvability. PLoS Biology, Vol. 4, 12, pp 2190-2193
This paper has not much to do with cancer but I have been interested in evolvability issues for a while so I decided to take a look at it. Tumour evolution has many but not all the features of the evolution involving longer time scales but its evolvability is not a thoroughly investigated topic. That is a shame because it seems that, given enough time, one would expect that tumour cells will not evolve only towards phenotypes that can take better advantage of the environment but also to genotypes that allow evolution to adapt better to that changing environment.
This paper does not explore this but something also interesting: that robustness and evolvability might be desirable but incompatible aims. Robustness can be seen as he ability to counteract change while evolvability represents the capability to adapt. In general it is true that species must strike some sort of compromise between these two abilities since organisms need the robustness provided, for instance, by the DNA repair mechanism but species need mutations that actually allow these organisms to better adapt to the environment. This is not always true and there are cases in which robustness and evolvability can go happily hand by hand. One such case is genomic redundancy. Up to a point, genomic redundancy improves robustness since functionality is kept in more than one location making it less vulnerable but also it helps evolvability since it allows duplicated genes to evolve different functions.
The general rule though is that organisms cannot be entirely robust to change in the form of genetic mutations since such an organism would freeze from an evolutionary point of view and thus subject to become extinct when a fitter rival comes around. I guess that that is a good explanation to cancer, a perfect reproduction mechanism would have not led from simple organisms to humans.
This paper has not much to do with cancer but I have been interested in evolvability issues for a while so I decided to take a look at it. Tumour evolution has many but not all the features of the evolution involving longer time scales but its evolvability is not a thoroughly investigated topic. That is a shame because it seems that, given enough time, one would expect that tumour cells will not evolve only towards phenotypes that can take better advantage of the environment but also to genotypes that allow evolution to adapt better to that changing environment.
This paper does not explore this but something also interesting: that robustness and evolvability might be desirable but incompatible aims. Robustness can be seen as he ability to counteract change while evolvability represents the capability to adapt. In general it is true that species must strike some sort of compromise between these two abilities since organisms need the robustness provided, for instance, by the DNA repair mechanism but species need mutations that actually allow these organisms to better adapt to the environment. This is not always true and there are cases in which robustness and evolvability can go happily hand by hand. One such case is genomic redundancy. Up to a point, genomic redundancy improves robustness since functionality is kept in more than one location making it less vulnerable but also it helps evolvability since it allows duplicated genes to evolve different functions.
The general rule though is that organisms cannot be entirely robust to change in the form of genetic mutations since such an organism would freeze from an evolutionary point of view and thus subject to become extinct when a fitter rival comes around. I guess that that is a good explanation to cancer, a perfect reproduction mechanism would have not led from simple organisms to humans.
Friday, February 09, 2007
Axelrod et al: Evolution of cooperation among tumor cells
R. Axelrod, D. Axelrod and K. Pienta: Evolution of cooperation among tumor cells. PNAS vol 103, 36, pp. 13474-13479, 2006.
A few months ago a friend of mine from Vienna send me the link to this paper (thanks Peter!) and although I skimmed through it at the time only now did I have the chance to read it with a little bit more of care. Robert Axelrod is well known in the complex systems and game theory communities. The research he did almost a quarter of century ago (detailed in his book: The evolution of cooperation) explained how cooperation can be established between two agents (people, elephants or cells) even when the mechanisms of the cooperation have not been agreed beforehand and the agents could gain more in the short term by not cooperating.
Now Axelrod and coauthors speculate on how this approach could be used to study carcinogenesis. They present this in the framework of Hanahan and Weinberg and the six capabilities required to progress towards cancer (self sufficiency in growth signals, ignoring anti growth signals, evasion of apoptosis, angiogenesis, limitless replicative potential and invasion/metastasis).
Now, this paper is no regular paper. Most research papers I read describe a particular piece of clinical research (we have investigated this gene in this context...), mathematical or computational model (in this paper we introduce a model that explains the influence of acidity in...) or are review papers. This one does not describe new clinical research nor does propose a formal way to describe any aspect of oncology nor represents a review of carcinogenesis research from the cooperation point of view. This is not meant to be a criticism. The paper represents for me a new category of papers, one whose aim is not as much as telling finished research as to suggest to the reader new venues of research under a particular perspective.
If that was indeed the aim then this is a good paper. According to the authors, the conventional view on tumor progression using the Hanahan and Weinberg framework is that cells have to acquire all the six capabilities but under the new cooperation based view this is no longer necessary. It could be possible that, at least some of this capabilities are provided by some cells to others and thus cancer could occur when groups of cells displaying a mixed set of capabilities collaborate to create the same effect of a single cell acquiring all the capabilities and reaching fixation (taking over the tumour population) by clonal expansion. One of the things that I was not very comfortable with is that the authors state that cancers are the result of genetic (or epigenetic) instability. Readers of this site probably know that this is currently a hotly debated topic (something as fundamental such as: what starts carcinogenesis) and that in front of the Weinberg school (cancer starts from genetic instability) is the , say, Tomlison school (a bigger number of cells and selection suffices to explain the start of cancer). My view is that if tumour cells can cooperate in order to share capabilities and progress down the path of carcinogenesis then having a higher mutation rate might not be so relevant and thus a cooperation based view on cancer would favour the view that cancer does not really need genetic instability to get started. If this view of mine turns out to be a stupidity remember that you read it here first.
The paper provides a number of examples of capabilities in which cooperation can happen. In angiogenesis (where cells can produce growth factors that benefit not only the producing cell but others in the neighbourhood), self sufficiency from (certain) growth signals (there is a certain amount of growth signals which can be produced in paracrine or autocrine fashion) and in invasion/metastasis (collaboration to degrade the ExtraCellular Matrix).
The authors point out that this view of carcinogenesis arises a number of new research questions such as what are the resources that can be shared among cooperating tumour cells, what mechanisms are used to share these resources, how does this affect the order in which mutations appear (since mutations can appear in parallel)? Interesting questions but it might take some for someone to come with the answers...if it is that answers can be found using evolutionary cooperation.
A few months ago a friend of mine from Vienna send me the link to this paper (thanks Peter!) and although I skimmed through it at the time only now did I have the chance to read it with a little bit more of care. Robert Axelrod is well known in the complex systems and game theory communities. The research he did almost a quarter of century ago (detailed in his book: The evolution of cooperation) explained how cooperation can be established between two agents (people, elephants or cells) even when the mechanisms of the cooperation have not been agreed beforehand and the agents could gain more in the short term by not cooperating.
Now Axelrod and coauthors speculate on how this approach could be used to study carcinogenesis. They present this in the framework of Hanahan and Weinberg and the six capabilities required to progress towards cancer (self sufficiency in growth signals, ignoring anti growth signals, evasion of apoptosis, angiogenesis, limitless replicative potential and invasion/metastasis).
Now, this paper is no regular paper. Most research papers I read describe a particular piece of clinical research (we have investigated this gene in this context...), mathematical or computational model (in this paper we introduce a model that explains the influence of acidity in...) or are review papers. This one does not describe new clinical research nor does propose a formal way to describe any aspect of oncology nor represents a review of carcinogenesis research from the cooperation point of view. This is not meant to be a criticism. The paper represents for me a new category of papers, one whose aim is not as much as telling finished research as to suggest to the reader new venues of research under a particular perspective.
If that was indeed the aim then this is a good paper. According to the authors, the conventional view on tumor progression using the Hanahan and Weinberg framework is that cells have to acquire all the six capabilities but under the new cooperation based view this is no longer necessary. It could be possible that, at least some of this capabilities are provided by some cells to others and thus cancer could occur when groups of cells displaying a mixed set of capabilities collaborate to create the same effect of a single cell acquiring all the capabilities and reaching fixation (taking over the tumour population) by clonal expansion. One of the things that I was not very comfortable with is that the authors state that cancers are the result of genetic (or epigenetic) instability. Readers of this site probably know that this is currently a hotly debated topic (something as fundamental such as: what starts carcinogenesis) and that in front of the Weinberg school (cancer starts from genetic instability) is the , say, Tomlison school (a bigger number of cells and selection suffices to explain the start of cancer). My view is that if tumour cells can cooperate in order to share capabilities and progress down the path of carcinogenesis then having a higher mutation rate might not be so relevant and thus a cooperation based view on cancer would favour the view that cancer does not really need genetic instability to get started. If this view of mine turns out to be a stupidity remember that you read it here first.
The paper provides a number of examples of capabilities in which cooperation can happen. In angiogenesis (where cells can produce growth factors that benefit not only the producing cell but others in the neighbourhood), self sufficiency from (certain) growth signals (there is a certain amount of growth signals which can be produced in paracrine or autocrine fashion) and in invasion/metastasis (collaboration to degrade the ExtraCellular Matrix).
The authors point out that this view of carcinogenesis arises a number of new research questions such as what are the resources that can be shared among cooperating tumour cells, what mechanisms are used to share these resources, how does this affect the order in which mutations appear (since mutations can appear in parallel)? Interesting questions but it might take some for someone to come with the answers...if it is that answers can be found using evolutionary cooperation.
Monday, January 01, 2007
Merlo et al: Cancer as an evolutionary and ecological process.
L. Merlo, J. Pepper, B. Reid and C. Maley. Cancer as an evolutionary and ecological process. Nature reviews cancer, Vol 6, pp 924-935, December 2006.
New year and (maybe not so) old traditions: the review of a paper. Nature reviews cancer is one of the world's top scientific journal in terms of impact factor for a reason: they publish very interesting and comprehensive reviews in a field of such importance and as crowded as cancer research. Review papers are comparatively more likely to be cited than the ones about one group's research, review papers in cancer research are normally highly cited since there are so many researchers working in the field. Review papers in a prestigious journal like Nature reviews cancer are thus bound to be cited once and once again and one would expect that only very good scientists would be invited to write for them (I believe that is only by invitation that you get to publish in these journals).
This review covers a topic that is very close to my interests: cancer from an evolutionary and ecological point of view. This view sees a neoplasm, a tumour, as a population of cells with a diversity of inheritable features. This means that evolution will happen and the fitter phenotypes will tend to be more abundant in the tumour population. Questions that might arise are how to alter the mutation rates, clone expansion and how does this expansion happen. Furthermore, given that in many cancers we can find mutations in vast areas of DNA, how do these cells retain enough genetic material to even function? The authors put forward the idea that this could be because most of the human genome is devoted to the development and homeostasis of a multicellular body and thus has no effect on the survival of the single cell in a tumour.
Having a diverse range of individuals whose uniqueness is inheritable is only one of the requirements of evolution. The other one is selection. In a tumour we have two sources of selection. Natural selection is the one that takes place in any tumour when there is scarcity of resources (oxygen, glucose, space). Under these circumstances some phenotypes are bound to be better at surviving and dividing than others. Additionally there is artificial selection which is the result of a therapy applied to a patient with a tumour. Artificial selection changes the fitness landscape, hopefully in such a way as to make survival impossible to every tumour cell. Unfortunately that is somewhat difficult so in many situations is worth altering the fitness landscape in ways that promote the survival of the least aggressive (that is, less likely to be able to invade and metastasise) tumour cells. In any case, altering the fitness landscape in favour of the patient is significantly easier when the tumour did not have much time to evolve.
Evolution in a tumour is not entirely the same as the one in organismal populations. That is to be expected given that tumour evolution lacks something of great importance: time. That is why during chemotherapy, surviving tumour cells are not the ones that develop mechanisms to resist but the ones that due to other reasons (genetic drift for example) already had the capability to resist before the therapy was used. Other differences include the reliance on stem cells for population diversity or that reproduction is asexual (which, incidentally, makes mathematical treatment much easier).
If a tumour resembles an ecosystem we should expect things such as cooperation, competition or parasitism. It seems that you get some of that. Like in an ecosystem individuals compete for the available resources (there is some speculation about that in the paper from Tomlinson reviewed the 10th of October of last year). There are predators if we understand as predation the behaviour of the cells from the immune system when they meet tumour cells. There should be parasitism, mutualism and commensalism (although the authors provide no evidence for that).
I found this a very nice and readable paper. I think it will make a good introduction to any cancer researcher that wants to study the evolutionary aspects of it. My only criticism of a paper that claims to deal with cancer as an evolutionary and ecological process is that the ecological part is significantly weaker than the evolutionary one.
Tuesday, October 03, 2006
Richard Dawkins interview
Nice interview in BBC of Richard Dawkins. Here he talks about his latest book The god delusion. Will be buying it as soon as it comes to Dresden (which is unlikely to be any time soon :().
Find the interview here
Find the interview here
Thursday, September 14, 2006
Review: "From artificial evolution to computational evolution: a research agenda"
A group of people whose work I respect (Dr. Miller was examiner at my PhD viva and I met Prof. Banzhaf in EA conferences) have recently written a paper entitled "From artificial evolution to computational evolution: a research agenda" that was published in the latest Nature Review Genetics (vol 7, page 729): http://www.nature.com/nrg/journal/v7/n9/full/nrg1921.html
Despite the journal in which they decided to publish it, the paper is addressed mainly to computer scientists working in the field of evolutionary computing. Researchers in this field use algorithms inspired by evolution in order to solve problems of optimisation in all sorts of field of engineering. Say you have to find the parameters that optimise a set of equations. If you encode these parameters into a string of number and create a bunch of these strings initialising them with random values you can use selection and crossover to find values that optimise the equation. Since not all the strings will produce the same results in the equation, we can discard the worst performing ones and fill the space they left with variations of the best performing ones. If we iterate this algorithm a number of times, thus producing successive generations of the initial population of strings, we are likely to obtain sets of parameters that, if not optimal, will likely to be fairly close to it.
This neat idea of using evolution in engineering (or even in art! I know a few examples of people that have used evolution inspired algorithms to produce music or paintings) has produced some interesting results but several people have already found that the very simplistic interpretation of evolution that computer scientists and engineers use in their algorithms is no match for the real thing. Real natural evolution (as opposed to artificial one) is both creative and open-ended.
Banzhaf et al identifies some of the shortcomings of traditional evolution-inspired algorithms and proposes a number of improvements framed in the new context of Computational Evolution (CE). This seems to consist, mainly, on adding extra bits of reality in the abstraction of evolution used by engineers and computer scientists in order to provide evolution with some complexity to play with. By doing this, for instance embedding it into analogue electronic circuits, they hope that artificial evolution will be successful were it was not before: solving ill-defined open-ended problems.
While I entirely agree with the idea that the original evolution-inspired algorithms could be significantly improved by enriching the stuff on which evolution works more complex and life-like, I am not sure that what they suggest is so ground breaking as to call the field a different name. Besides, many of the suggestions mentioned have been in use by computer scientists (especially the authors of the article) for some time (for example: more biologically plausible genotype-phenotype mappings, on which people like Peter Bentley or Julian Miller have done very useful work).
In any case I would not like to sound as if I did not like the paper. I did and I think that despite some further objections (such as: why don't they explain why the bits of nature that they decided to pick are the really necessary ones?). Actually I would like to join my voice to theirs and suggest a further use of computational evolution - A more realistic model of evolution can be used not only to do engineering but also to study evolution per se. I would definitely be interested (and in a way that is what I do for a living) in using Computational Evolution to study evolution from a theoretical perspective.
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