molecular biology of the X-gene, pt. 2

following the last post, i will now provide the first of many hypotheses for what the actual molecular mechanism of how the X-gene makes people “mutants” in the Marvel universe.  to restate the question more specifically, how is it that variation in a single gene (the X-gene) can give rise to the range of variation that we observe in Marvel mutants?

[full disclosure: this is the hypothesis that i favor, in part because it matches the data in my opinion, in part because of my affiliation with one of the leading research groups in this area.]

a major area of research in real-world genetics is in arguing about what the contributors are to the heritability of various human traits, or phenotypes.  for instance, height is known to be very heritable- if your parents are tall, you are likely to also be tall.  if your identical twin is short, you are likely to be just about the same height.

[(c) gloooscap]

however, no one has found a ‘tall gene’, per se.  people have found lots and lots of genes that seem to have a very small contribution to height.  but even when you add these all up, they come nowhere near explaining the observed heritability of height.  why this is so, is not so clear.

one speculative but very interesting argument for why this is the case is that we are thinking about the problem incorrectly.  specifically, when we attempt to estimate the effect of each gene, we are making the assumption that the same genetic variants (“alleles”) have the same effect in each person.  this is called the “additive” model, because it implies that you can just add up the effects of each gene to predict how tall someone will be.  there will be some effect of the environment too (“nurture”, see figure).

we pretty much know that the additive model is wrong.  the reason we use it is that it’s so dang easy, especially when you’re working with millions of different locations in the genome.  however, there are some clever ways that you can still more or less make the assumption of additivity, but skirt some of its problems.

one way that has been proposed is to sort people before you do your study- into categories of “robust” and “non-robust”.  the thinking here is that the non-robust folks are more susceptible to the same variation.  this means that any effect of genetics on the trait in question is amplified, whereas in the robust folks, they shrug off the effects of genetic variation very easily, because the rest of their genetic program is so tightly controlled.  consequently, much of the variation in height that we observe might just be non-robust people who are hyperresponsive to heritable variation.

real-life examples of robustness

the idea of robustness has some convincing empirical support.  for instance, here are some plant (Arabidopsis thaliana of the Ler type) seedlings:

[(c) Nature, Queitsch et al. (2002).  letters indicate different organs- for instance, l=true leaf, c = cotyledon/seed leaf]

GDA is a drug that takes away a plant’s normal robustness (we’ll get into why in a sec).  the letters label various organs.  as you can see, the plant on the left is totally screwed, whereas the plant on the right is nice and symmetrical and obviously has structures like stems and leaves.

here are some more images of the same sorta thing, except that in addition to GDA there is another method of perturbing robustness (RNAi), with different examples of “lost robustness” in two columns on the right:

[(c) Sangster et al. (2007), PLOS One (CC-BY).  defects in each panel: A: anthocyanin (purple pigment) accumulation, B: dwarfing, C: asymmetry and missing leaf, D: asymmetry and extra leaf, E: overgrowth of leaf hairs (trichomes), F: defects in meristem and leaf primordia, G: asymmetry and split leaf, H: asymmetry, I: heart-shaped cotyledon (seed leaf), J: many defects.]

as you can see, all these non-robust plants are wacky.  the interesting thing is that they are all wacky in different ways.  they are all technically clones (genetically identical), but even so, they respond to the perturbation in quite different ways.  it has also been shown that adding small amounts of genetic variation to the equation makes non-robust phenotypes even weirder.

the bizarre, variable effects of the loss of robustness have also been shown in fish and flies, among other organisms.  thus, we can expect that similar effects will be observed in humans with disrupted robustness.

in each of these instances, robustness was compromised by the same manipulation: screwing with the protein Hsp90 (stands for “heat shock protein that weighs about 90 kilodaltons”). every multicellular organism (in addition to most bacteria) have this protein.  Hsp90’s job as a protein is to take care of other proteins- it helps them fold properly.  so when you take away Hsp90, suddenly you have a lot of half-folded proteins lying around, still trying to do their functions but not getting them exactly right.

so it makes a lot of sense why hitting Hsp90 will have lots of off-target effects.  when you hit Hsp90, you’re really hitting about 10% of the proteins in a cell, no matter whether it’s a human cell or a yeast cell.  why exactly this leads to so much variability in form and organ function is still not understood, largely because there are so many disparate, occasionally contradictory effects.

the question is, are there other Hsp90s out there?

are the X-men non-robust?

so let’s bring this back down out of the clouds into comics.  let’s recall some facts about the X-men mutants:

  1.  they all vary from the human norm in different ways
  2. all of these differences are attributed to the action of an active version of the X-gene
  3. these effects are not necessarily (though occasionally) heritable, but the active X-gene is heritable.

this sounds a lot like the Hsp90 example i just laid out.  so, in brief, one hypothesis is that the X-gene is just another kind of Hsp90 (recall that proteins are encoded by genes), with a function in controlling the robustness of human development.  in this view, the “active” X-gene is a version which has reduced robustness, whereas most people walking around are non-mutants with an X-gene that properly controls robustness.

this solves a fair number of problems:

  • explains the dramatic variation of mutant forms
  • derived from the effects of a (imaginary) single gene
  • explains low heritability of specific mutant powers, but high heritability of being a mutant
  • works with the X-men + Marvel canon of mutant biology

the evidence against:

an honest scientist (e.g. not a scientific racist or a member of unnamed large consortia) will generally consider alternatives to a hypothesis under study.  in this spirit, i have tried to present some arguments against the hypothesis that the X-gene is a robustness gene:

  1. most of the experimental manipulations to screw with Hsp90 in the lab aren’t heritable (they consist of drug treatments).
  2. could such non-robustness be heritable in the wild? the heritable manipulations consist of artificial transgenic approaches involving, for instance, RNA interference (RNAi).  these are extremely unlikely to arise spontaneously in natural populations.
  3. wouldn’t natural selection work really hard against any mutation which messed with Hsp90?

these are all coherent objections.  a couple of years ago, people identified natural fly populations with naturally-occurring mutations of Hsp90.  these mutations did in fact seem to interfere with Hsp90 function.  this seems to overcome objections (1) and (2).  such Hsp90 variants exist in the wild.  however, when competed in the lab against other flies with normal Hsp90, or subjected to high temperatures, flies with these mutations rapidly went extinct.

thus, (3) is a robust argument against the existence of an X-gene that behaved like Hsp90, and was yet capable of giving rise to the wondrous specimens of the X-men (thanks rob liefeld).

however, we have previously established that, in the Marvel universe, mutations don’t happen like they do in the real world.  i would continue to argue that, in light of the directed mutagenesis that seems to be the case for the X-men, the X-gene remains a plausible robustness gene.

you are, of course, free to disagree with me.

next up: is the X-gene a mutator?

Quickly

hello readers, the few the proud. i know that i haven’t posted for a while, for which there are a variety of reasons. one reason is that i wanted to emphasize quality over quantity, and to only make posts that have real ideas behind them.

another reason is that i got interested in the issue of scientific racism last year and spent some time focused on researching its intersection with mainstream genetics and genomics. that doesn’t exactly align with the point of this blog, but i thought that nonetheless it made sense to cross post a draft of that work here: https://medium.com/@iusewords/scientific-racism-and-the-human-genome-b5c86d3c6751

please let me know if you have any comments or ideas.

i have another comics-oriented post in the pipeline, fear not. i expect it will take another month or two before i have time to focus on it.

thanks.

molecular biology of the X-gene, part 1

[i just franklined jim watson]

the x-men are proving (as i might have predicted if i’d thought about it) a particularly rich vein of material, so i’m going to continue posting on them. the X-men is a comics franchise with a long tradition of preposterous scientific back-stories.  i do not condemn it for this reason, but for the sake of posterity it is necessary to examine exactly what ‘mutants’ are in the real world and in the comic, and how the “X-gene” can be examined from the perspective of modern molecular biology.  by thinking critically about genetic outcomes in the real world vs. the marvel universe, hopefully we can come to a better understanding of how biology is working in both cases.  i have treated the phenomenon of mutation in a previous post.  in this and future posts i will attempt to deal with the X-gene itself, and how it relates to the differences between mutants and ‘normal’ people in the marvel universe. i am somewhat disappointed to not be the first to go for this topic, but i think that a more holistic treatment of the subject is warranted.  however, i cannot state (like some) that marvel should dispense with the X-gene for its lack of realism.  the truth is that there are multiple semi-plausible genetic hypotheses for the effects of the X-gene, as i hope to illuminate in this post.  in the earliest incarnation of the comic, it was stated that mutant powers came not from general mutagenesis of the genome, but rather from their acquisition of something called the ‘X-gene’, on top of their homo sapiens genetic material. this explanation got steadily more sophisticated with time.  from the horse’s mouth:

(c) Marvel

admittedly, the matter does seem to get a bit jumbled.  but the overall implication is that there is some sort of sex-linkage.  here, beast implies that the gene resides on the X chromosome (traditionally considered the 23rd chromosome in addition to the 22 autosomes, though in practice never referred to as such). for a short discussion of X-gene inheritance, see my previous post.  what certainly seems to be the case is that the mutation is ‘dominant’.  that is, inheriting a copy of a mutant X-gene from only one parent seems to be sufficient to give rise to phenotypically ‘mutant’ offspring.

beast offers us an explanation: a ‘mutant’ X-gene is actually a mutator gene.  it goes off and takes a whack here and a whack there in the rest of your genome, and then you end up with wings.  this interpretation dovetails nicely with the observation in my last post that, in the marvel universe, the (largely) rejected hypothesis of directed mutation is actually true.  thus, the X-men usually don’t have cancer, morphological defects, metabolic disorders, and neurological/intellectual disorders, which are the real-world consequence of high rates of mutagenesis in humans.  instead, they have generally ‘beneficial’ mutations which give them powers beyond the ken of homo sapiens sapiens. we can call this the “mutator hypothesis”.  there are several real-world examples of “mutator” strains.  cells maintain a preposterously complex system of safeguards to prevent and repair mutations, and knocking out a piece at many points in this system will lead to higher rates of mutation (for one popular example, see MSH2).

mutations tend manifest around the same time as secondary sexual characteristics, at least for people who aren’t already morphologically outside the human norm.

(c) college humor

so there’s some variation, but basically ‘mutant’ phenomena are coincident with normal parts of human development (look out for a later post on this).  normal human development involves a lot of cell divisions, which gives time for mutations to happen, manifest in different tissues, etc.

this is all very well and good.  it seems like a logically coherent explanation for how, in the marvel universe, people end up looking like beast. but let’s take a step back.  there are several possible objections:

  1. whatever beast says a mutant is will be retconned in five years for short-term benefit and is thus not necessarily true.
  2. beast may be wrong in his interpretation (recall that mutant genetics is an active field of research).
  3. beast is obviously speaking in laymen’s terms to laymen.  perhaps he is simplifying his explanation for the sake of clarity. he may still be speaking only facts (high mutation rate, the pleiotropic effects of the X-gene), but not faithfully articulating the actual causal chain which leads to the observed phenomenon (himself).

there are alternative biological explanations which can use the same set of facts to come to the same phenomenon, and they don’t even (necessarily) depend on my silly directed mutation idea. i will use future posts to discuss various possibilities.

possibility vs. plausibility

an important distinction to keep in mind is that what i will discuss are hypotheses, not things anyone believes to be true (we are talking about comics, for chrissake!). a hypothesis is, at its most basic level, an explanation that is not inconsistent with fact.  but the lack of impossibility does not mean that a given hypothesis is believable.  for instance, organismal evolution is not a hypothesis- it is a dominant theory, because it has the support of reams of empirical data and a mathematically rigorous underpinning.  my hypotheses have neither.  they are what we call “just-so stories“: logically possible explanations that have no intrinsic merit.

all of them are wildly unlikely when you compare them to our ‘data’, i.e. the actual manifestations of ‘mutants’ in Marvel comic books.  you will have to decide for yourself which hypothesis or hypotheses are the least-bad.  and then, when new data and new thinkers come, there will be new hypotheses, which are a little less bad.  science is a bridge and not an end.

is inheritance of the mutant X-gene incoherent?

a brief post devoted to a puzzle (likely best to ignore).

according to marvel continuity, the X-men ‘mutant’-determining X-gene is a sex-linked gene. there is some confusion among fans and official sources about how exactly it works, though (also here).  that leaves X-linkage and Y-linkage as possibilities. furthermore, it’s supposed to be dominant, i guess.  okay.  X dominant or Y dominant.  let’s follow this.

1) can’t be Y-linked- women are mutants, but they don’t have a Y chromosome.

2) can’t be X-linked- men pass it on to their sons (Wolverine and Draken, Magneto and Quicksilver [in some continuities]).

3) probably not dominant- the Guthrie family repeatedly gives rise to mutants, despite the fact that the parents are not mutants.

can it still work?  maybe we will have to abandon dominance. but the X and Y do actually show regions of homology (where they are basically the same chromosome) to one another- intro genetics will tell you that this is necessary for proper meiosis.  the regions of homology in humans are called the pseudoautosomal regions (or PARs; autosomes are non-sex chromosomes, so these are the small regions where the sex chromosomes behave like non-sex chromosomes).  however, the structure, organization, and even presence of these regions are not constant throughout human populations. that is, mom can have one arrangement of her PARs, and dad can have another.  recombination between mom and dad’s unequal PARs can give rise to yet more weird PAR organizations, such that you inherit PAR-residing genes in a non-intuitive fashion.

could we then state that the X-gene is in one of these PARs? thus, in some cases (where homology exists between parents) it is passed on as if autosomally.  where the PARs are organized differently between the parents, this will restrict recombination between X and Y, leading in some cases to patterns of inheritance that will look like Y or X linkage, and sometimes not. this would also explain why the pattern of inheritance varies between mating pairs.

granted, i know no example of a trait showing these patterns of inheritance in the real world, and the PARs are relatively small regions of these chromosomes.  but my main concern is showing how these thought experiments can force us to reason rigorously through these phenomena, with full possession of the facts, rather than react without reflection (like some of the blog posts linked to above).

may do a follow-up on the dominance question.

update:

recent study on recombination in the pseudoautosomal region (or rather the biggest of them: PAR1): this is interesting because it suggests that 1) recombination is much more intense in this region than others, and 2) selection is acting more strongly here than elsewhere in the human genome.  unclear what the relationship is between these phenomena.

update update:

see yet another paper on the PAR, this time about variation throughout humans!

the origin of mutants

[with apologies to john cairns and colleagues]

the idea of mutation and of ‘mutants’ is of course not a new one in the sense of genetics- it dates to the early days of the discipline in the late 19th century, well before anyone had discovered or proposed nucleic acids (DNA) the material basis of inheritance.  it certainly predates the x-men.  however, i would make a substantial bet that if you ask 5 people on the street what they think of when you speak the word, 4 would say (if they were honest) “the x-men”.  i would argue that the x-men comics (and their spinoffs) have a unique power in controlling how people think about the science of genetics.

[copyright steve thomas and welovefine.com]

the one time i went to a comics convention (emerald city comicon 2009, for those of you who are keeping track), there was a talk that was purportedly along these lines, given by a dude from a small college in las vegas i believe.  however, the dude clearly didn’t know much about  biology or its literature. i believe he was some kind of cultural anthropologist, who made the mistake of good-naturedly opening the floor to an audience discussion after about 5 minutes of material.  comics fans, for all their ardor, get into a muddle in these situations quicker than you would believe.  i left halfway through, quite dissatisfied.

history and the x-men

the origin of the X-men can be best understood in light of 1963, when it first came out.  the threat of catastrophic nuclear war was a constant backdrop to life.  thanks to herman muller, it had been known for years that radiation exposure in adult flies could cause heritable morphological aberrations (‘mutations’) in their offspring, which weighed on people’s minds in the presence of hiroshima, nagasaki, and constant nuclear testing.  however, the mechanistic basis of these changes was only hazily understood by leading scientists, and probably not at all by stan lee and jack kirby.  however, they would have been abundantly aware of  scientists (including muller) publicly voicing skepticism about the wisdom of using technologies involving large doses of ionizing radiation, given their known dangers as mutagens and teratogens.

[https://theconversation.com/animals-in-research-drosophila-the-fruit-fly-13571: two mutant fruit flies.  the left fly has the ‘Curly’ mutation which changes wing morphology, the right fly has the ‘white’ mutation, that prevents the normal red pigment from coloring the eyes.]

[a series of well-known Drosophila melanogaster mutants: http://www.bio.miami.edu/dana/pix/]

i am having a bit of difficulty figuring out exactly where the mutants came from in the original x-men (need to get ahold of a collection of those first few issues!), but i would again bet a sum that their sudden outbreak was explained by the relatively new explosion of nuclear technology- after all, the 18-year-old mutants in 1963 would have been born around the time of those first nuclear weapons deployments in 1945, concordant with a layman’s understanding of muller (though the timing doesn’t quite work out for them to be heritable “germ-line” mutations, rather than simple teratologies- embryonic defects).  there are  several x-men-related products that are called “children of the atom“.  charles xavier and magneto are less neatly accounted for, but doubtless some explanation can be contrived.  there is actually a gratifyingly complete timeline interlacing x-men chronology and the progress of genetic research on the “x-men: first class” movie timeline (or maybe a fan wiki of some kind?).

 

[copyright Marvel.  note jean grey flapping her hands uselessly in the background while the dudes get stuck in.  thanks 1963!!]

why do some mutations happen and not others?

while lee and kirby may have heard of muller (who was, after all, a bit of an activist and public intellectual with a dramatic political biography and a 1946 nobel prize- he is on the timeline mentioned above), i doubt that they knew of luria and delbrück (whose nobel prize took till 1969, and who are not on the timeline).   that link is not to a wikipedia page talking about them, but rather to a version of their 1943 paper that was the first empirical contention in a long and fraught intellectual debate over how organisms actually acquire mutations.

the debate is concerned with an ambiguous observation: when mutants are isolated, their mutation tends to adapt them better to the environment from which they are isolated.  there were a number of competing explanations for this observation.  luria and delbrück belong to one camp, which for lack of a better term i will call the ‘darwinian’.  this camp argued that mutations occur randomly throughout the genetic material, and that favorable variants are selected thereafter by natural selection, in line with classic darwinian predictions.  this mechanistically explains why favorable mutations are found at higher frequencies than deleterious ones- it is essentially an articulation of the tired ‘survival of the fittest’ trope.

another camp, which i might call the ‘lamarckian’, was dissatisfied with this explanation.  they preferred a more intriguing possibility: when placed in an environment, organisms will selectively mutate themselves in ways that assure higher fitness in that specific environment.  while mechanistically less clear, this theory had the compelling argument that, by the same ‘survival of the fittest’ trope, any organism which possessed this trait would have a massive advantage in fitness over an organism behaving as the ‘darwinian’ camp suggested: it would 1) not have to risk possibly disadvantageous mutations in its adaptation to new environments, and 2) not have to depend on the passive process of mutation to generate variants. this would obviously be massively more efficient process of adaptation.  it also would provide a powerful arrow in the quiver of evolutionists in their larger cultural debate against creationists and the like: creationist ideologues to this day frequently cite the horrendous inefficiency of darwinian evolution as an argument against its capacity to produce the obvious diversity of life (‘irreducible complexity’ in the creationist verbiage).  this hypothesis came to be known as “directed mutation” (bolded because i’m going to use this term from now on).

hopeful mutants

i would contend that the x-men arose directly out of this tradition of directed mutagenesis.  firstly, one of the proponents of directed mutagenesis was a german geneticist named richard goldschmidt.  while doing pioneering work in a broad set of disciplines, he also developed a theory of evolution based on the appearance of sudden large changes (‘saltation’), drawing on observations of morphological mutants that occur under stressful conditions.  this was popularized as the ‘hopeful monsters‘ hypothesis, which with some notable exceptions has mostly been an object of satire in the scientific community.

[i first heard of the “hopeful monster” hypothesis because it was referenced in my favorite vonnegut novel, “Galápagos”, as the inspiration for a kilgore trout novel called “The Era of Hopeful Monsters”.  i would recommend this as a fantastic book for thinking about the evolutionary process, particularly as deconstructing the notion of humans as somehow inviolate within biological evolution, and as a counterpoint to the dogma of constantly increasing complexity.  incidentally, in this book there is also a “hopeful monster” child born to a mother who was at nagasaki when it was bombed.  so this is not necessarily a unique trope…]

 the basic idea is that when environmental circumstances change dramatically, organisms sense this somehow and go into mutational overdrive, trying to produce some form that could be properly adapted for the new environment (not always wrong). however, ‘hopeful monsters’ is exactly what the x-men are.  almost every mutant in the marvel universe is an independent mutation, and represents a unique form.  the mutants are startlingly polymorphic, considering that they are all put in the same bag (i have a post in prep on this subject).  amusingly, this has not escaped the creationist community, who have used it as a straw man for the wacky stuff that those evolutionary biologists come up with.  there’s also a great flickr account that comes up when you google ‘x-men hopeful monsters’.

starting with magneto’s genocide trip, a constant theme in the series is a sort of a struggle between humans and mutants (as if they were different)- homo sapiens vs. ‘homo superior’:

this subplot is latched onto by grant morrison in his run on the “new x-men”.  he gets very interested in this duality as a parallel to the supposed destruction of homo sapiens neanderthalensis by homo sapiens sapiens, in a very explicit fashion.  i think i could write a post just about how the sapiens-superior vs. sapiensneanderthalensis comparison (and maybe i will, some day):

[copyright Marvel]

this narrative is intensified by his invention of something called an ‘extinction sequence’ in the homo sapiens genome, which is just what it sounds like.  how exactly this sequence is missing from homo superior genomes, which in the comics arise constantly from homo sapiens, is not clear.  quibbles aside, morrison puts the icing on the cake of a world where the directed mutation of mutants make perfect sense.  under the new environmental regime of accelerating societal and technological change, the weirdo mutants are not only favored but destined to succeed over plain old humans.  they do so not from a single lineage, as predicted by darwin, but as a set of independent directed mutations from humans, as predicted by goldschmidt.  furthermore, there is no evidence of mutation that is ‘random’ with respect to fitness; essentially every mutant who makes it onto the page is, in some respect, stronger, faster, smarter, or otherwise given a leg up on humans, and none of them have the silly ‘extinction sequence’.

note that this does not necessarily make the mutants more ‘fit’, per se, in the terms of evolutionary biology (i.e. high reproductive success).  however, all the evidence is that they are more fit in the ways that a popular audience would expect.

consequently, the x-men live in a world that has a system of genetics that operates by directed mutation.

luria and delbrück on mutation

luria and delbrück (L&B) wanted to design an experiment that would distinguish between the two hypotheses of random mutation vs. directed mutation in the real world.  the experiment itself was a simple one, but with a somewhat complicated interpretation: the two hypotheses give rise to somewhat different expectations as a direct response to selection.  as their model system, L&B used E. coli and a virus that kills E. coli, T1 phage.  people knew that bacteria treated with T1 gave rise to resistant mutant E. coli at a low rate.  the question was whether T1 resistance was a trait that arose randomly in the population before T1 (“spontaneous”, or the darwinian hypothesis), or whether the bacteria chose T1 resistance as a mutation in response to the virus (“induced”, or the directed mutation hypothesis).  see figures below to distinguish between the two hypotheses:

Luria-delbruck_diagram_stars

[wikipedia: two hypotheses for mutation, showing cell lineages for four experiments each.  blue cells are normal E. coli, whereas red cells are T1-resistant mutant E. coli.  the last branching generation generation is the one exposed to T1 phage selection (brown). pink stars and arrows indicate when mutations happen under each model (and how often). note that in the directed mutation model, all mutations happen after exposure to T1.]

as you can see, there is a somewhat different statistical rate of mutation between these two hypotheses.  basically, the spontaneous hypothesis predicts that there is much higher variation between experiments (spontaneous: “exponentially distributed”; induced: “poisson-distributed”, for you technical folks).  by doing a number of well-controlled experiments, L&B were able to show that the distribution of mutations was closer to exponential than to poisson, and thus that these mutations were likely to be random mutations in the population before T1 exposure, rather than mutations arising in response to T1.

exp_vs_pois

[comparison of the expected results from the two hypotheses across 10,000 simulated experiments – note that the yellow (stochastic) distribution is much wider than the blue (induced), though both distributions have the same mean.  for some reason the overlap between the two distributions is sometimes rendered as gray and sometimes as green, sorry.]

[note that the actual experiment was not so neat.  basically, salvador luria had performed a bunch of experiments on his own, where he noticed that in most experiments there were no mutants, but in a few experiments there were a very large number of mutants.  

he likened this to playing a slot machine- most of the time you get nothing, but every now and then there’s a really big payout.  this is because some cultures of bacteria will randomly have the T1-resistance mutation occur, and then this mutation will be propagated until there are many mutant cells in the population, all prior to T1 exposure.  however, most cultures will simply not give rise this mutation.  this is different from the expectation from induced mutation, which is that there are lots of small payouts and no jackpots, because you would expect the mutation to always arise at the same rate in response to T1 infection. consequently, as long as you had roughly the same number of cells in each culture, you would get the same results across cultures.  

while luria had this intuitive understanding, he had trouble with the mathematics that were needed to demonstrate his hypothesis, so he went down the hall to the office of the physicist (and later, famous molecular biologist) max delbrück.  delbrück was able to formalize the expected results in terms of the poisson and exponential probability distributions, which gave luria a very specific quantitative hypothesis to test.]

real-world score: darwin 1, directed mutation 0.

this was not the end of the debate, of course.  there was still substantial debate over the quantitative contribution of different models of mutation, but the terms of the debate had been shifted dramatically in favor of the more mechanistic (but less sexy) theory of spontaneous darwinian mutation.  for a fuller (technical) discussion of ensuing research, i recommend this writeup.  but luria and delbrück had articulated a general model which can explain the vast majority of cases of mutation, is in line with conventional genetic theory, and shows a robust mechanism.   

consequently, we can say that the real world and the world of the x-men actually function according to different biological laws.

the x-men comics are not ‘wrong’

the function of science fiction in society (besides, of course, enjoyment) is to take the scientific ideas and technology in currency, and to extend them into thought experiments.  these alternative worlds allow us to deal practically with the idea of a future, and to view our own world with a ‘defamiliarized’ eye (to drag shklovsky into it).  the creators of the x-men took (and still take) the ideas of muller, goldschmidt, and others (probably not directly!) and tried to imagine a world where humans are biological objects that are subject to mutational processes.  that they got these processes wrong according to the technical literature of their own time is neither here nor there- they built a world that allows us to understand our own better.

i enjoy reading the x-men as an escapist genre- don’t get me wrong. sometimes comics can just be read as comics. however, i think that the modern world owes a debt of gratitude to the x-men for making us actually think about about biology and evolution, even if there’s a bunch of half-baked pseudoscience thrown in. and biologists, i believe, can come to a better understanding of what they do by being forced to consider these alternate worlds, and to really think about what distinguishes them from our own world.

this post was intended to be a section of another post on the biology underlying the x-gene, but as soon as i started giving it any serious thought, it became clear that this topic was going to blow out of proportion.  the other post will appear at a later date.

i dedicate this post with thanks to my teachers RHW and JAS for introducing me to this fascinating topic in their class.

 

the filth

i thought i’d kick this off with a heart-warming and not science-heavy exercise.  at some point i will probably follow up with some sort of statement of intent for why i’m doing this blog, but it’s unlikely that anyone other than me will ever look at it, so i want to get right to it.

grant morrison has sort of made a genre for himself of, as he says in the preface to his first “Animal Man”, ‘absolute unreadable gibberish that has… become my stock-in-trade’.  said gibberish usually seems to revolve around paranoia, occultism, crackpot science, metatextualism, and bizarre teams of heroes fighting for vaguely anti-authoritarian causes.

while i think that his description is not a bad characterization of the content of his comics, i would add that it does not describe his appeal.  while it’s fun to watch king mob shoot his way through beetle-soldiers while wearing a weird hat, what continually draws me to pick up morrison’s comics is rather his treatment of love.  

as a person who generally has a lot of difficulty expressing his emotions, this feels very weird to say.  however, what really gets me in morrison’s work is the way that he portrays relationships between humans and animals (and in “We3”, between animals and animals).  however much trouble i may have relating to people sometimes, i have never had any difficulty getting very silly  and wrapped up with animals.  in particular, morrison and i seem to share a totally unreasonable love of cats.  why on earth would anyone ever associate with cats?  they need to be fed, they shit in a box which you have to clean, they either ignore you or irritate the crap out of you, and they strain your relationships with people whose adaptive immune systems make bad decisions.

morrison’s position on human-animal relations can be taken from the horse’s mouth in his last issue of “Animal Man”, where he writes himself in as a character.  he reveals that much of his motivation in writing the comic had been driven by his personal empathy towards animals.  the treatment is (as his fantasy simulacrum admits) somewhat heavy-handed in places, and he makes a shameless plug for PETA of the counterproductive practices.  but it’s hard not to be moved by the simple passion that he evinces for the subject, which he continues mining as an inspiration throughout further work (like the heartbreaking “We3”). 

i just reread “The Filth”, my third trip through, this cloudy saturday afternoon.  the reason i keep coming back to “The Filth”, despite the excessive scatology and tedious hypersexuality, is its touching portrayal of the relationship of a man with an animal.  while hardly a new idea, this relationship is lent poignancy by its juxtaposition with the madcap life of the protagonist’s alter ego (not to mention his porn addiction).  this man is offered and sometimes coerced into a james-bond life of wild colors and intrigue and hot willing babes, but all he wants is to return to his lonely bachelor life with a sick cat.

[(c) grant morrison, chris weston, gary erskine]

one can only hope that the person sitting next to me didn’t notice my undignified sniffling when i got to this panel from the second-to-last page:

wehavelove

 

[(c) grant morrison, chris weston, gary erskine], apologies for poor quality.

while this invites an unfortunate comparison to that one scene in “Everything You Ever Wanted to Know About Sex But Were Afraid to Ask”, i find it to be completely delightful.  if the physiological bureaucracy of my body were aspiring to one thing, i would hope that it’s something like this.

i suppose that i could get wrapped up in whether or not the endocrinology of the text is plausible, but that seems seems to me to be beside the point.  most of this comic (see title) works off the theme of bodies being disgusting, as producers of waste, and as messes to be cleaned up.  what this page shows us is that we have been ignoring the temple for the sake of the midden out back.  the body is a beautiful system which is competent on its own to generate our most noble impulses and actions.  of course we are also machines that produce shit, as Da Vinci famously noted.  but Da Vinci was a machine too.  this is further symbolized by the mysterious boss, ‘mother dirt’, who appears to be an animated compost heap.  she gives the protagonist a heaping handful of herself:

Feeley/Slade (holding up sickening blob): What am I supposed to do with this?

Mother Dirt: Spread it on your garden, Greg.

and after this, there are inexplicable hothouse flowers growing out of the sidewalk in every panel.  i think it’s great.

this is the point of this blog and the point of why i do what i do every day.  cue a well-known quote from our friend charles:

“There is grandeur in this view of life, with its several powers, having been originally breathed into a few forms or into one; and that, whilst this planet has gone cycling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved.”

most fundamentally, think of a man with a cat.

having exposed myself as a hopeless sap, i bring this first post to an end.