If you can find the time too read the this, I am looking for feedback. Rough Draft. Lengthy but interesting; the main gist is in the second to last section. Introduction “We, and all other animals, are machines created by our genes” -Richard Dawkins To begin, I would like it to be noted that I am a subscriber to the “Selfish gene theory”. That is, I believe that our bodies are no more than complex structures capable of chemical manipulation which are designed to transport and propagate our genomes. Everything we do, from sexual urges, to operant behavior, and perhaps a large amount of actions that we consider to be driven by “free will” are in fact done to suit the survival of our genes. In an oversimplified analogy, we are to our genes as a vehicle is to us. A second strong belief I have along with much of the scientific community is the idea that Charles Darwin, although certainly a brilliant naturalist, was not entirely correct. Rather he just scratched the surface of evolution and speciation. This should come as no surprise as his theories are over a century old and were formulated with no knowledge of genetics. . Now, as I said before, it is my opinion that the human body is nothing more than a machine created in order to keep a certain genome alive. We are equipped with advantageous tools such as the ability to alter our environment and the ability to form complex cognitive processes. These are no different from other tools that different genomes employ to ensure their survival such as claws, teeth, and physical girth. I refuse to believe that these abilities and attributes are the eventual product of random chemical interactions between proteins that happened to become refined. The main reason which I believe that genetics is not purely based on errors in sequencing is because every living creature has one thing in common, a drive to survive and pass on their genes. This essential ‘urge’ exists in all forms of life and has not been diluted or enhanced through billions of years of natural selection. Whether by the result of either chance chemical reactions or perhaps something profoundly deeper, there is no doubt that humans have evolved to a point where we are self aware and can form advanced cognitive processes. What interests me is that our genes encode for a sort of fail safe to these abilities. That is, it appears that our cognitive resources are available for the purposes of bettering our lives and ensuring our survival, but we are still not in complete control of our very bodies. There are unconscious processes within the depths of our brains that control all vital tasks and put us in line if we threaten to interfere with them. An easy example of this is how it is impossible for one to suffocate his or her self merely by holding their breath. A person can hold their breath for a long amount of time if they are determined enough but eventually they will pass out. This is a response by the autonomic nervous system. Your brain renders you unconsciousness so that you cannot consciously inhibit respiration and you begin to breathe normally while asleep. This is an eerie reminder that no one is in complete control. In my opinion the best ways to observe the extent that your unconscious processes have over your conscious ones are in the cases of neurological disorders. One example occurs in a rare disorder called “foreign limb sensation”. This occurs when the brain becomes convinced that a certain body part, such as a hand, does not exist. Thus when it receives input from receptor cells on the fingers of the “missing” hand it experiences a crisis. A conflict is created in the mind of the affected where the unconscious processes, which believe that there is no hand, are pitted against the conscious mind, which is very aware that there is definitely a hand present. This battle is almost always won by the unconscious processes (which I will for now on refer to as our “unconscious” for the purpose of length). The patient spirals into a temporary psychotic state which results in them crudely removing that hand with an axe or other tool. Thus the goal of the unconscious was achieved despite how completely irrational and insane the thought was to the conscious mind. Obvious exceptions to this are suicides and effective repression of sexual drives which occur as a result of a large variety of situations. The main point to take from this is that a given body is an extension of its genome and thus functions and develops at its will. The Hierarchy of Sciences “The so-called Pythagoreans, who were the first to take up mathematics, not only advanced this subject, but saturated with it, they fancied that the principles of mathematics were the principles of all things” -Aristotle Another principle which is an important basis to later arguments is the hierarchy of sciences, or the idea that each major science is a subset of another. Consider biology. Biology exists in a world governed by chemical reactions. More specifically, biology is chemistry; everything within a given biological system is the result of or the representation of complex biochemical reactions. Thus biology is a subset of chemistry and the laws of chemistry govern those of biology. Now consider chemistry; all chemicals, be they elemental or complex, neutral or ionic, organic or inorganic all have specific chemical properties. These properties are governed by interactions between subatomic particles which behave the way they do because of their physical properties. Thus chemistry is governed by the laws of and is a subset of physics. Now physics is a tough one. What science could possibly envelope physics? The answer lies in a discipline not considered by all to be a true science. It is physically impossible to write down an exact value for the transcendental number Pi. Yet it appears everywhere in our physical universe. It is impossible to track every digit of Pi because we are restricted by the physical universe while the number is not. It exceeds physics. Think of any physical law you can, it’s all a specialized form of math, just as chemistry is a specified form of physics and biology a specific form of chemistry. Physics is a subset of and governed by mathematical law. Thus, by transitive properties, biology is a subset of as well as governed by math. And it is! I do not think I need to explain how math is extremely prevalent in biology. This will become important in later discussions later. The Great Escape “If there is one thing the history of evolution has taught us it's that life will not be contained. Life breaks free, expands to new territory, and crashes through barriers, painfully, maybe even dangerously.” -Michael Creighton (Jurassic Park) Not too long ago, biochemists proclaimed an end to cancer after the initial success of the drug imatinib in the selective elimination of certain types of leukemia via inhibition of mutant tyrosine kinases. Their joy, however, was short lived. Bacterial cells and viruses are able to quickly develop resistance to antibiotics because they divide rapidly and their rate of genetic mutations and subsequently evolution is much more rapid than multicellular organisms with large, complex macrogenomes. More specifically they’re able to quickly vary their genotypes. Thus via natural selection and other driving sources they are able to correct their genetic weaknesses that antibiotics target; predominantly by sheer chance resulting from brute force tactics (similar to a hacker entering every possible arrangement of letters into a computer until he finds the password). Tumor cells can behave in a very similar manner. Tumor cells also divide rapidly (it is actually their rapid rate of division that makes chemotherapy an option) and the same scenario develops. The renegade genetic strain ‘recognizes’ that imatinib is taking it down and corrects for it via Darwinian evolution; resulting in an imatinib resistance and thus the need for researchers to develop new drugs. This is amazing. The genes behind cancer are no exception to my ideas that every gene species possess a drive to survive. Once the genetic strain has mutated into a cancer cell, it has, in my opinion become a sort of subspecies of the human genome. The human genome eventually recognizes this and attempts everything within its limit to destroy the cell. In a perfect world, the tumor strain would allow its destruction for the betterment of the species of a whole. But it doesn’t. It is its own species, and it does not want to die. Thus it divides as quickly as possible to prevent its extinction and gain a numerical edge, and sends out colonizers throughout the blood stream to establish a presence. All of these actions often result in the death of the host and subsequently the gene. Thus it is a tragic destiny, a depressing story for the gene with only one ending. It is a microcaual example of perhaps a hostage taker trying to make it out alive, or of a malevolent civil war faction. As novelist Michael Creighton reiterates above, life and thus genetics always finds a way. Thus it is plausible that an oncogene might somehow derive a mechanism to excise itself from its host genome and maybe even escape the cell. One possible method to export a genetic sequence from the cell would be through an ancient vector, mRNA. This would require much outside help. For one there would need to be a large variety of enzymes, some of the more important ones being proteases, integrases, and, the most crucial, reverse transcriptase to transcribe the sequence from RNA to DNA in order to recreate the genome after escaping. But the tools are there. Proteases are fairly common throughout the average cell while integrase is very similar to proteins used in post-transcriptional modification in eukaryotes. But what of reverse transcriptase? It is there as well. Recent studies show that cancerous cells show excessive telomerase activity, an enzyme used to create repetitive ‘buffer zones’ at chromosomal ends to prevent a progressive degradation during replication. This is important because one of the subunits of telomerase is none other than a form of reverse transcriptase. So, is it not feasible that an oncogene may have managed to utilize these resources to successfully convert into mRNA and escape via a primitive vector such as a piece of membrane from the host cell? If so, could it reintegrate itself into a separate host as does a virus? If this were the case, we would expect to see a class of viruses whose genetic material consists of mRNA and causes cancer like symptoms when integrated into a new host. Say hello to the retrovirus. Although most renowned as the causal agent of AIDS, retroviruses are responsible for a wide variety of diseases in many mammalian species. Interestingly enough, the majority of these diseases associated with them are cancers such as sarcomas and leukemia. Therefore it is possible that retroviruses are not as ancient as biologists once assumed, but rather a product of the eukaryotic genome. Of course it is also possible that modern retroviruses picked up the necessary equipment for their escape left behind in our systems by endogenous retroviruses. The fact of the matter is that retroviruses are not unique. Genetic elements are continuously removing themselves and re-integrating into our genomes in the forms of transposons, DNA viruses, RNA viruses, endogenous retroviruses, naked DNA and so on. Our genome, along with the genome of every other complex organism (i.e. not viruses) is not a steady code but rather a dynamic population with elements immigrating, emigrating, and mutating at a steady rate. The sum of these actions, supplemented by Darwinian factors, culminates in the driving force of evolution. Integral Theory of Evolution “God created man in His own image, and behold, it was very good. And the evening and the morning were the sixth day.” -GENESIS 1.27, 31 A close inspection of our genome reveals a dynamic world populated by mobile sequences of nucleic acids. It is the result of millions of years of addition, subtraction, and competition amongst these sequences that has made our DNA the way it is today. The integrative theory of evolution is very hard for me to sum up in a single sentence so instead I will attempt to do so through a simplified timeline of how I believe our genomes came to be what they are today. I believe that initially there was RNA. I do not know how or why it came to be I just postulate that it was the first of the nucleic acids. RNA, once synthesized and differentiated into various forms by whatever means, had an amazing ability. It could manipulate its chemical environment through the production of proteins. The more proteins that were created, the more resources that could be utilized and also for construction of additional proteins or other biomolecules such as lipids, sugars, etc. As these RNA’s consumed and produced more and more, they developed to such complexity that they could be viewed as a proto-organism. However, a single RNA sequence can only form so many proteins, and thus different RNA sequences found interdependence to be a survival advantage in that they could each benefit off of each other’s specific proteins. This development led to the first colonial RNA proto-organisms. This presented a problem however, as all proteins being expressed from all RNA sequences at once would lead to chemical chaos and ill fortune to the colony as a whole. It thus became necessary to find a way to organize the sequences into a system by which only certain factors would be expressed at once through the help of outside proteins. Through simple redox chemistry, the first DNA sequences were born. These sequences were in fact populations of different incorporated factions. As the sequences and necessarily the biomolecular structures surrounding, nourishing, and maintaining them became more and more complex with the integration of more and more stray sequences, complex biochemical pathways became a necessity. As these genomes grew in size, various factions began to fight for expression by multiplying or translocating themselves within the sequence. This natural competition, Darwinian in nature, lead to increasing specificity among different genomes as certain factions gained a survival advantage over others and dominated parts of the genome. Also complexity began to increase as more sequences entered the genome. The end results were the first prokaryotic cells, now with complex mechanisms for integrating new DNA (transformation and conjugation) and also affected by the constant immigration and emigration of various genetic elements through transduction and viral escape respectively. The power of the combined actions of the dynamic genetic populations within genomes to induce evolution I will for now on refer to as integral forces. It did not stop there. Following suit of the genetic elements within them, prokaryotic cells found survival advantage in numbers and thus the first multicellular colonial organisms were formed. Eventually barriers between individual cells were broken down and genomes combined through integration into macrogenomes. The result was the first truly eukaryotic cell. As a further mechanism of controlling the actions of so many different factions, sequences which no longer expressed proteins relevant to the community to the whole were inhibited by a new system of post-transcriptional modification; splicing. These eukaryotes began to move into the vastly different directions that integral forces took them and differentiated into the various forms we see today, one of which is man. These genetic populations continued to compete for expression and thus resources amongst each other, leading to the synthesis of complex ecosystems. Other transient sequences evolved into obligate parasites and made use of occasional chemical mistakes, Darwin’s random mutations, to evade the biological defenses of the far more complex macrogenomes they infected; leading to the first viruses. The evidence that our genomes are a collection of smaller ones is there. We still hold the genes which transcribe features of earlier organisms, such as skeletal structures or organs, within our DNA. Occasionally these sequences proliferate throughout our genome and evade splicing, thus managing to be expressed in the form of vestiges. The sum of this theory is that it is the integral forces that play a large part in evolution. Darwinian evolution is there, but is minor in comparison, with the exception being in organisms with smaller genomes. This idea of integration repeats itself through the complexity of biology. Early RNA factions grouped together and integrated to form the first DNA sequences, which grouped together and integrated into the first prokaryotes, which grouped together and integrated into the first eukaryotes. Even in society we see how our genes influence social interactions. The first people grouped together to form communities which grouped together to form towns, nations, and empires. In fact, global society today appears to be an accurate macrocosm of our genomes, bringing home the idea that we are what out genes make us. Also, nucleic acids still utilize and manipulate the resources of their environment, in one particular strain they do so through a complex biological structure known as a man, which is the result of an ordered expression of RNA sequences leading to the production of various proteins. It is eerie to note that we are a manifestation of our genes, made in their own images, one might conclude. Genetic Excellence “But we have soothed ourselves into imagining sudden change as something that happens outside the normal order of things. An accident, like a car crash. Or beyond our control, like a fatal illness. We do not conceive of sudden, radical, irrational change as built into the very fabric of existence. Yet it is.” On closer inspection it seems ignorant of me to criticize Darwin’s theories due to the fact that the way I believe genomes behave is very similar to Darwin’s observations of ecological systems. In both situations constituents compete for survival and the sum of their actions results in a change in a system, be it a genome or an ecosystem. The real problem I have with Darwin’s theories, which I also believe were nothing short of genius given the knowledge and equipment he had to work with, is the assumption that mutation and natural selection is influenced by ‘randomness’. I previously described the hierarchy of sciences. By this reasoning it can be deducted that genetics is governed by math. When applied to the integrative theory, it initially seems as if our genome can be treated as a massive polynomial equation. Obviously, factors such as frame shifts, deletions, excisions, etc. negate such an elegant belief in the end. However, these seemingly random events can still be explained through math; more specifically though chaos theory. That being said, it is my belief that the genome is a dynamic system which is the result of a series of complex chaotic equations. That which appears random is in fact governed and predicted by math. The significance here is monumental. If the genome were in fact governed by an equation or system of equations, then like any other math problem, it could be factored or reversed to find the original state of the system. This, if possible, could potentially lead to a myriad of discoveries, one of which would be how old our genome actually is. Genetics, along with neuroscience, is a fairly recent field which holds a plethora of secrets pertaining to our existence. As with any science, the field will witness the ebb and flow of theories as new ideas are bolstered and dismantled in light of evidence. Every discipline of science eventually experiences a revolution in which the ways of thinking are completely reversed. In physics, beliefs have been smashed and reversed with revolutionary ideas such as those of celestial orbits, relativity, and quantum mechanics. I believe genetics is overdue.
