The human [cess]pool

    Everybody wants life liberty and the pursuit of happiness. Everybody. Though most people will tell you this is a fantastic situation, leave it to me to tell you otherwise. This is a problem. No, not at first. At first it's good...almost euphorically good. But eventually, should this continue to be the status quo, this will become a problem (and, likely, already is). How, you ask, could such a wonderful system that feeds cripples and delinquents love and bunnies be anything but THE BEST SYSTEM IN THE WORLD? Well, for one, because it makes everyone praising the wonders of America sound like a bunch of raving lunatics who can't logically understand the nature of a country on a global scale, but that's nothing new to humanity. No, the real problem lies in the nature of our relaxed system and how it may affect our biological future.

    As humans begin to fully understand the nature of what they are, several things are becoming clear. For one, nobody wants to admit what all fields of science (you know, that mumbo-jumbo that gave you TVs, computers, vaccinations, and almost everything else you cherish) are blatantly telling us. That humans are animals, derived from animals, and are where they are today (evolutionarily and biologically speaking) due to specific selective pressures applied to our ancestors. Pressures that equipped the standard human for specific tasks, imbued him with unprecedented information-sharing (and cooperative) capabilities, and endowed him with the tools to become the most successful replicating machine on a whole planet of successful replicating machines. Invariably, everything we learn from our history, biology, and surroundings (ie physical environment) screams that we are nothing more than extremely adept replicating machines who can trace our origins back to an event in earth's early history (assuming life started on Earth) where several molecular regimes began replicating themselves and haven't stopped since. Naturally, they accrued data as they went—both in the form of external inputs and internal inputs (life-on-life competition/interaction)—, evolved new methods of information-exchange, and redirected certain pressures to form different “units” under selection, but the basic principles are all the same, and the initial replication event was what set it all in motion. So, though amplified, glorified, and self-deified, humans are nothing more than replicating machines operating under various evolutionary pressures (molecular evolution, natural selection, ect), and all that they do and are is the product of said pressures, experienced throughout their evolutionary history.

    All of that is old news. Any self-respecting biologist will pay lip-service to these concepts (though many only casually accept them), but only a few vehemently and fully believe and understand them. Under the above assumptions egalitarianism is far-from good. What egalitarianism does is pander to the individual, based upon each human's inherent aversion to subjugation—at least openly; many humans freely accept social subjugation—, desire for freedom from impending death, and other universal (or near-universal) needs. These needs, however, are simply biological imperatives fixed within our population through natural selection (see above), and, as any slightly logical person can see, rightfully so. The human aversion to subjugation is the product of the nature of the selfish psychology of a genetically-independent individual (contrast to the members of a eusocial network), the aversion towards death is an obvious product of how detrimental failing to have said aversion was to our less-than-fit ancestors (you know, the ones that didn't have that self-preservation instinct), and all of our other shared needs (the human need for love/companionship, the human need for religious belief, ect) hold a similar evolutionary origin—which I will not get into here; for more on these UTFSE. Ultimately, humans desire these things because having these desires was advantageous to our ancestors and, depending upon the prevalence of an ideal, provided varying levels of fitness to those with them (both, as a function of group and individual fitness). This leads us to the inherent problem within egalitarianism, its incompatibility with the nature of an organism/population of organisms.

    As we develop more and more epigenetic therapies (ie. therapies that leave the underlying genetics of those treated unchanged) for malady with our society, and apply them nearly-universally, we are relaxing the pressures that have been in place for all of life's history. As covered above, an organism is the product of physical pressures placed upon its species and population; and a population of organisms is constantly in genetic flux, as this is one of the mechanisms at the root of life's ability to churn out novelty. Mutations create variations on the organism's genetic code which are then acted upon by external pressures in the form of selective death. Some mutations have little effect (termed synonymous mutations) due to the fact that more than one DNA triplet can code for the same amino acid, while others alter the amino acid sequence of a protein (missense mutations). Some of these sequence-alterations have only minor effects on the protein product (termed quiet mutations) while others have detrimental effects (such as in sickle-cell anemia). There are far more variations on how a mutation can effect change in an organism and how transposable elements and other forms of molecular evolution can enact change, however this is not a dissertation on molecular evolution. Furthermore, traits (especially in more complex organisms) are usually the product of the interaction of many genes (polygenic) separated both spatially and temporally, and each represented by two copies (alleles) in an organism. Due to these factors many mutations only alter an organism's phenotype subtly and, should this alteration be beneficial, spread throughout the population quickly (thanks to sexual exchange, in many/most multi-cellular eukaryotes). All of these factors of life's biology lend to a species' ability to rapidly adapt to external pressures should the need and mechanisms arise, and, due to their often novelty-introducing nature, mutations are far from negative and far from uncommon—in fact, it is generally assumed that sex evolved largely to spread mutations about within a population. As such, a species is constantly being fixed in place by external and internal pressures, acting against one another in a delicate dance on the border between chaos and complexity/uniformity.

    One of the seminal assumptions of evolution is that, within a population, more organisms will be produced than can possibly mate in the next generation--thereby creating the "excess" information from which to 'select'—if only as many organisms were produces as were needed mutations would run havoc throughout the population, or, more likely, the species would simply die out. In many human societies however, this is no longer the case (or has been heavily relaxed), as almost all humans reproduce that wish it (though, granted, some do not for various reasons). Hopefully, at this point, you can see where this is going. As human society continues to relax the external pressures acting on the human organism, the internal pressures covered above (mutation, molecular evolution, ect) are able to run (partially) rampant, sowing misinformation throughout our genetic code and gravely “expanding” the human form (“alteration” can only occur with culling). With the physical constraints placed on the individual all but absent (morbidly obese and hopelessly frail humans can still, and do still, have families), there is nothing holding the human form "in place"--physically and, in many cases, behaviorally. This problem cannot rectify itself as no human will optionally give up their reproductive rights simply to see a brighter future for the human race (that they, genetically speaking, will no longer be a part of). This, ladies and gentleman, is the probable fate of the American dream—human dream, to be more accurate. As freedom increases and everyone is entitled to reproduction and health-care support (which is ever-improving to meet the needs of an infinitely entitled population) the inevitable problem of mutation and expansion continue to be overlooked or ignored.

     So, we see, life, liberty, and the pursuit of “happiness” doesn't necessarily have a happy ending (although, these predictions are, in no way, set in stone). The problem is that humans are still extremely reluctant to understand the picture painted so parsimoniously for us by biology, and as such, are nowhere near reaching a coherent understanding of their own bodies and species. This wouldn't be a problem if the USA wasn't a democracy, but, unfortunately, every moron out there gets a (admittedly partial) say in many matters. Instead of face the somewhat disillusioning music, they decide to ignore the discussion of evolution, the nature of an organism (as the product of selective pressures which define its genetic parameter-space), and how, without selective pressures, any population of organisms will (invariably) undergo extensive decay, due to the nature of information-sharing and novelty-induction (mutation, molecular evolutionary mechanisms, ect.) associated with sexual exchange and organisms in general. Naturally, there are still some constraints placed upon humans, but they are rare and often half-hearted (sexual assortment, other conditions we have yet to "excuse" through medical therapy). Much like how every use of an anti-biotic creates the potential for an evolutionary response in the target population of microbes, every epigenetic treatment for a pathology creates the potential for human genetic corruption—and though this “corruption” is already evident, should it continue it will have definite implications for fields such as health-care, where everyone is “equal” and entitled to service (a totally unsustainable situation). Add to this the fact that we are living in an almost certain statistical despotism (where what is popular is god, not what is right or logical), and what we find ourselves living in is not the American dream, but the American nightmare—BAZING!

    A note should be made that, though this note has a very prophetic, doomsdayesque feel, genetic understanding and techniques are improving (within the scientific community), and it is probable that many of these problems could be alleviated in the future through genetic “therapies”. However we are far from feasible, economic solutions, and, while scientific progress is often impressively rapid, no easy solutions are around the corner; especially considering the state of current public understanding. There will likely not be any measurable issues within our lifetime, but rest assured that these issues are real and will not go away simply because we pour ignorance over them.


--In a recent "Inaugural Article" in PNAS this was addressed, as well as some of the novel features of human genetics/the human genome associated with somatic-cell mutation throughout the human's life--relatively unrelated to the subject of this "note", as it addresses within-generation human mortality. While admitting that this concept is not necessarily a new one, the author state that "the enormous change in the selective environment that human behavior has induced during approximately the past century. Innovations spawned by agriculture, architecture, industrialization, and most notably a sophisticated health care industry have led to a dramatic relaxation in selection against mildly deleterious mutations, and modern medical intervention is increasingly successful in ensuring a productive lifespan even in individuals carrying mutations with major morphological, metabolic, and behavioral defects."

    They then go on to state that "the fundamental requirement for the maintenance of a species’ genetic integrity and long-term viability is that the loss of mean fitness by the recurrent input of deleterious mutations each generation must be balanced by the removal of such mutations by natural selection. If the effectiveness of the latter is eliminated, normal viability and fertility can be maintained to a certain extent by modifying the environment to ameliorate the immediate effects of mutations, but this is ultimately an unsustainable situation, as buffering the effects of degenerative mutations would require a matching cumulative level of investment in pharmaceuticals, behavioral therapies, and other forms of medical intervention. Given the relatively high human mutation rate and the fact that a relaxation of natural selection typically leads to 0.1% to 1.5% decline in fitness per generation in other animal species with lower mutation rates (51), this type of scenario has now gained a level of quantitative credence that was absent when Muller (49) first raised the issue." And finally, "although there is considerable uncertainty in the preceding numbers, it is difficult to escape the conclusion that the per-generation reduction in fitness due to recurrent mutation is at least 1% in humans and quite possibly as high as 5%"--note that these estimates do not account for the probable increase in mutagen-intake associated with modern human industrial society (processed foods, ect). The irony in all of this is the fact that the future of human genetic "purity" lies within the genomes of those in the least industrialized societies, where selection is still far less relaxed.






-Lynch (2010), Rate, molecular spectrum, and consequences of human mutation. PNAS 107(3): 961-968

intersection of ribozyme folds and support for neutrality

    Though recently many authors have argued that molecular neutralism (ie. the position that the vast majority of changes at the molecular level occur due to genetic drift of selectively neutral mutations) is 'on the rocks', this study provides resounding evidence for the continued support for the viewpoint (or, at least, a balanced viewpoint such as the one addressed by Wagner (2008)).

    The authors examine two ribozymes (ribonucleic 'enzymes') with grossly differing sequence (<25% identity--the human hepatitis delta virus self-cleavage ribozyme and a class III self-ligating ribozyme) and folding, and, through a 'mutational walk', succeed in transforming them into one another.

    Furthermore, they show that through most of the 'walk' the enzymatic activity of the mutated molecules do not change dramatically.  This supports the contention that neutral mutations that have little effect on the molecular function of proteins can accumulate during 'neutral' evolutionary activity (through synonymous or nearly neutral alterations in nucleotide sequence, or, in the case of proteins, functional substitutions), allowing single polymorphisms to have drastic effects on structure and function when paired with said neutral alterations.

    Finally, the authors further create 'prototype' molecules of each 'fold'-type that share nearly 100% sequence identity (the shift in folding occurs through the changing of 2 nucleotides), demonstrating that, even with highly similar (near-identical) sequence identity, highly different functions can manifest.  Taken, together these results demonstrate how specific molecules (namely, robust proteins or ribozymes) can undergo a large number of neutral changes while retaining largely stable functionality.  It is only when these nearly-neutral changes are paired with a single (or few) highly structurally significant changes that large evolutionary/functional changes can occur.  This may explain how many multi-step evolutionary changes come about despite several neutral (or even mildly deleterious) intermediate states that would not be intuitively fixed through selection alone.


-Schultes E and Bartel D (2000) One Sequence, Two Ribozymes: Implications for the Emergence of New Ribozyme Folds . Science 289: 448-452.
-Wagner (2008) Neutralism and selectionism: a network-based reconciliation. Nature Reviews: Genetics 9:965-974