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genes etiketine sahip kayıtlar gösteriliyor. Tüm kayıtları göster

Genes: convenient tokens of our time

My post today, perhaps typically cranky, was triggered by an essay at Aeon about the influence that the film Still Alice has had on thinking about Alzheimer's Disease (AD). As the piece puts it, AD is presented in the film as a genetic disease with a simply predictable doom-like known genetic cause.  The authors argue that the movie is more than entertainment.  It's a portrayal that raises an important ethical issue, because it is very misleading to leave the impression that AD is a predictable genetic disease.  That's because a clear genetic causation, and thus the simple 'we can test for it' representation, applies only to a small fraction of AD.  The film badly misrepresents the overall reality of this awful form of the disease (a good treatment of Alzheimer's disease and its history is Margaret Lock's thoughtful The Alzheimer Conundrum, 2013, Princeton Press).

While focusing on AD, the Aeon piece makes strong statements about our obsession with genes, in ways that we think can be readily generalized.  In a nutshell, genes have become the convenient tokens of our time.

Symboling is a key to making us 'human'
If there is any one thing that most distinguishes our human species from others, it may be the use of language as a symbolic way to perceive the world and communicate to others.  Symboling has long been said by anthropologists to be an important key to our evolution and the development of culture, itself based on language.

Symbol and metaphor are used not just to represent the world and to communicate about it, but also to sort out our social structure and our relationships with each other and the world.  Language is largely the manipulation or invocation of symbols.  In a species that understands future events and generalities, like death and sex, in abstract terms, the symbols of language can be reassuring or starkly threatening.  We can use them to soothe ourselves or to manipulate others, and they can also be used in the societal dance around who has power, influence, and resources.

Symbols represent a perception of reality, but a symbol is not in itself reality.  It is our filter, on or around which we base our interactions and even our material lives.  And, science is as thoroughly influenced by symbols as any other human endeavor.

Science is, like religion, a part of our culture that purports to lead us to understand and generalize about the world, but because science is itself a cultural endeavor, it is also part and parcel of the hierarchy and empire building we do in general, part of a cultural machinery that includes self-promotion, and mutually reinforcing service industries including news media, and even scientific journals themselves.

The current or even growing pressures to maintain factory-like 'productivity' in terms of grants coming in and papers going out is largely at odds with the fundamental purpose of science (as opposed to 'technology').  Unlike designing a better product, in the important, leading-edge areas of science, we don't know where we're going.  That is indeed the reason that it is science.  Exploring the unknown is what really good science is about.  That's not naturally an assembly-line process, because the latter depends on using known facts.  However, our society is increasingly forcing science to be like a factory, with a rather short-term kind of fiscal accountability.

Our culture, like any culture, creates symbols to use as tokens as we go about our lives.  Tokens are reassuring or explanatory symbols, and we naturally use them in the manipulations for various resources that culture is often about.  Nowadays, a central token is the gene.

DNA; Wikipedia

Genes as symbols
Genes are proffered as the irrefutable ubiquitous cause of things, the salvation, the explanation, in ways rather similar to the way God and miracles are proffered by religion.  Genes conveniently lead to manipulation by technology, and technology sells in our industrial culture. Genes are specific rather than vague, are enumerable, can be seen as real core 'data' to explain the world.  Genes are widely used as ultimate blameworthy causes, responsible for disease which comes to be defined as what happens when genes go 'wrong'.  Being literally unseen, like angels, genes can take on an aura of pervasive power and mystery.  The incantation by scientists is that if we can only be enabled to find them we can even cure them (with CRISPR or some other promised panacea), exorcising their evil. All of this invocation of fundamental causal tokens is particulate enough to be marketable for grants and research proposals, great for publishing in journals and for news media to gawk at in wonder. Genes provide impressively mysterious tokens for scientists to promise almost to create miracles by manipulating.  Genes stand for life's Book of Truth, much as sacred texts have traditionally done and, for many, still do.

Genes provide fundamental symbolic tokens in theories of life--its essence, its evolution, of human behavior, of good and evil traits, of atoms of causation from which everything follows. They lurk in the background, responsible for all good and evil.  So in our age in human history, it is not surprising that reports of finding genes 'for' this or that have unbelievable explanatory panache.  It's not a trivial aspect of this symbolic role that people (including scientists) have to take others' word for what they claim as insights.

This token does, of course, have underlying reality
We're in the age of science, so that it is only to be expected that we'll have tokens relevant to this endeavor.  That we have our symbols around which to build other aspects of our culture doesn't mean that the biology of genes is being made up out of whole cloth.  Unlike religion, where things can be 'verified' only by claims of communication with God, genes can of course, at least in principle, be checked and claims tested.  Genes obviously do have major and fundamental roles in life.  If that isn't true, we are really misperceiving fundamentals of our existence.  So, even when complexities of causation are daunting, we can claim and blame what we want on genes and in a sense be correct at least at some level.  That enhances and endorses the token value of genes.

Genes do have great sticking power.  The Aeon piece about AD is just one of countless daily examples.  A fraction of cases of AD are so closely associated with the presence of some known variants in a couple of genes, that true causation--whatever the mechanism--seems an entirely plausible explanation.  Likewise, there are hundreds or thousands of disorders that seem clearly to be inherited and as the result of malfunction of one or two specific genes.  The cultural extension of this in our society that we are stressing here is the extension of these clearly causative findings to the idea that causation can be enumerated in convenient ways mainly by peoples' inherited genomes and that other aspects of biological causation are often treated as being rather superficial or incidental.  That in a sense is typical of deeply held cultural icons or tokens.

The problem with genes as tokens is that they are invoked generally or generically in the competition for cultural resources, material and symbolic.  Personally, we think there are issues, genetic issues in fact, that deserve greater investment, rather than just the easier to invoke bigger-is-better approach. They include a much more intense attack on those many traits that we already know without any serious doubt are tractably genetic--due to one or only a couple of genes, and therefore which real genetic therapy might treat or prevent effectively.  By contrast, most traits even if they are affected by genetic variation as all traits must be, are predominantly due to environmental or chance causative factors.  We have ways to avoid many diseases that don't require genetic approaches, but as vague entities they're perfect subjects for invoking the gene token, and policy in the industrial world clearly shows this.

Some progress does of course occur because of genetically-based research, but the promise far outpaces the reality of genetic cures.  But genes are the material tokens that keep the motor running far beyond the actual level of progress.  They effectively reflect our time--our molecular, computer, technological culture imagery, our love of scale, size and the material grandeur they generate.

Every culture, every generation has its tokens and belief systems.  Genes are among ours.  They're never perfect.  People seek hope, and what velvet robes and gilded cathedrals and mosques provide for many, whereas the humming laboratories do for a growing number of others.

Tokens, symbols and metaphors: they drive much of what people do, even in science.

Running and neurogenesis; the plastic brain

A new paper online in the Journal of Physiology ("Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained," Nokia et al.), and described here by the NYT, reports that running is good for the brain.  At least the rat brain.

From the paper (emphasis mine):
Adult hippocampal neurogenesis (AHN) is a continuous process through which cells proliferate in the subgranular zone of the dentate gyrus, mature into granule cells, and ultimately become incorporated into hippocampal neuronal networks. In rodents, adult-born hippocampal neurons seem crucial for a variety of adaptive behaviors such as learning, pattern separation, and responses to stress. Aerobic exercise, e.g. running, increases AHN and improves cognitive performance in both male and female adult rodents. The increase in AHN in response to running is reported to be in part due to an increase in the number of surviving neuronal precursor cells (type 2) rather than to the shortening of the cell cycle. There are also studies indicating that running increases the survival and incorporation of newly divided hippocampal cells, born days before commencing training, to increase net neurogenesis. [See the paper for citations for reported findings, which I've removed here for length.]
It has already been well-established that aerobic exercise is associated with an increase in adult hipocampal neurogenesis, the number of neurons in the hippocampus, the region of the brain associated with producing long-term memory among other functions.  But, Nokia et al. wondered if it was only aerobic exercise, or whether other kinds of exercise have the same effect.

So they compared the number of neuronal cells of mice subjected to high-intensity interval training, resistance training and distance running.  They found no increase in the rats who did resistance training compared to sedentary rats, and a smaller than expected increase in rats that did the interval training.  It was only in the brains of the rats who did aerobic exercise that neurogenesis was significantly increased.  The authors hypothesize that this is because running stimulates the production of  brain-derived neurotrophic factor and insulin-like growth factor, which are associated with neurogenesis. The more aerobic exercise the animal does, the more of these the animal produces, and thus the more neurons.

Currently the best advice for preventing dementia in old age is to maintain a social life, quit smoking, and exercise.  And, if this rat study can be applied to humans, this should at least qualify that as aerobic exercise; running or biking, say.  As with all such lifestyle advice, this surely won't work for everyone, but the evidence is increasingly in its favor, at least on a population basis.

But there are deeper implications of this work, I think.  If exercise changes the architecture of the brain in ways that can affect learning, even in adults, and, as has been repeatedly demonstrated, stimulating children by reading to them, using lots of words, playing music to them, and so on, or the reverse, growing up in poverty,  or with disease, or amid famine all can affect brain architecture and thus cognitive ability for better or for worse, why do so many continue to privilege genes and genes alone -- or even more, a single gene -- for the creation of intelligence?



Source: "Effects on brain development leading to cognitive impairment:  A worldwide epidemic," Olness,
Journal of Developmental & Behavioral Pediatrics:
April 2003 - Volume 24 - Issue 2 - pp 120-130

It seems that the brain responds to experience at all ages, but it's possible that there's a 'sensitive period' for cognition.  As just one example, the cognitive abilities of children reared in institutions in Bucharest were compared to that of children never placed in an institution to those whose lives began there but who moved to foster care before age two.  Those who were reared entirely in institutions had much lower cognitive ability than the other two groups; the cognitive abilities of those who were moved to foster care before age two significantly improved.  The authors of this study suggest that there may be a sensitive period for developing cognitive ability, just as there is one for learning language, and many other aspects of brain function.

Of course, as with any trait, genes play a crucial role in the development of the brain.  But they don't do it alone.  E.g., a 2010 paper in Child Development describes the genetic underpinnings of the developing brain, but its plasticity as well.
The foundations of brain architecture are established early in life through a continuous series of dynamic interactions between genetic influences and environmental conditions and experiences (Friederici, 2006; Grossman, 2003; Hensch, 2005; Horn, 2004; Katz & Shatz, 1996; Majdan & Shatz, 2006; Singer, 1995). There is increasing evidence that environmental factors play a crucial role in coordinating the timing and pattern of gene expression, which in turn determines initial brain architecture. Because specific experiences potentiate or inhibit neural connectivity at key developmental stages, these time points are referred to as sensitive periods (Hess, 1973; Knudsen, 2004). Each one of our perceptual, cognitive, and emotional capabilities is built upon the scaffolding provided by early life experiences. Examples can be found in both the visual and auditory systems, where the foundation for later cognitive architecture is laid down during sensitive periods for basic neural circuitry.  
Genetic determinists might acknowledge the plasticity of the brain but then say that how the brain responds to experience is what's genetically determined, and thus that there are children who just aren't genetically equipped to be the next Einstein, or even to learn calculus.  We know this is true at least at one extreme of the distribution of intelligence, because there are many alleles known to be associated with low cognitive ability.  These usually cause syndromic conditions, however, so aren't related only to how quickly synapses are crossed, or memories made, or whatever it is that underlies -- or defines -- intelligence.  As with many other trait distributions, what happens at the extremes doesn't necessarily represent what's going on in the middle, so I think the jury is still out as to the overriding importance of single or even a small number of alleles in the development of normal or above normal intelligence (again, whatever that is -- for the moment, let's call it the ability to score well on IQ tests).  And indeed no genes with large effects on intelligence have yet been identified, despite decades of looking.  That has so far included comparison of the tails of the distribution among individuals without a clear-cut pathology.

So, of course there are genes involved in how quickly people think, or make connections between ideas, or memorize, or invent things, or remember -- how people learn.  But it's not either mainly genes or environment.  It's both, interacting, and molding the reactive brain.  There is enough evidence now to show that the brain is a hungry organ, soaking up and responding to experience at all times, throughout life.  Whether or not we believe that society should be investing in optimizing the environment of every child to maximize their potential is a social and political decision, not a scientific one.

Rare Disease Day and the promises of personalized medicine

O ur daughter Ellen wrote the post that I republish below 3 years ago, and we've reposted it in commemoration of Rare Disease Day, Febru...