Immortality And The Gilgamesh Project (cancer research)

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http://www.nexusmagazine.com/articles/GilgameshProject.htmlThe Gilgamesh ProjectBy Andrew Sokar slowsubversionWith multiple awards to his name for cancer research, this childhood prodigywas silenced when his forbidden science began closing in on the secret ofeternal life.The ability to deal effectively with diseases such as cancer and theconsequences of the ageing process remains one of the last major challengesfor biomedical science. In order to meet this challenge, it is pivotal that weunderstand the underlying mechanisms for the cell growth cycle, i.e. why cellsgrow and divide, why they undergo a process known as differentiation(why and how identical embryonic cells become mature liver, skin, brain cells,etc.) and why, ultimately, cells lapse into senescence and die, causingthe metabolic decline and death of the organism.Problems such as these have obsessed me since childhood and have fired apassionate interest in chemistry and biology long before I enrolled in myfirst college chemistry course. Considering the extreme human, social andeconomic costs of diseases such as cancer, heart disease and illnessesassociated with advancing age, I could be forgiven for thinking during my highschool years that a career devoted to solving these problems was the noblestpursuit possible. If someone had told me that vested interests did not wantsolutions to these most pressing of medical problems, I would have consideredthem a delusional conspiracy nut. However, my experiences have me permanentlydisabused of this notion.In this article, I wish to relate the incredible odyssey that has been my lifeand some details of the medical research that I have undertaken. I believethat this research, if taken to its logical conclusion, stands a good chanceof yielding non toxic treatments for various forms of cancer and also forprolonging the human life span, possibly indefinitely. Instead of beinglauded for these achievements, I have had my education and career in themedical sciences derailed and my life essentially ruined.There are many lessons to be learned from my experiences that would be worthyof a Hollywood thriller. The first is just how precariously close we stand tobringing the fountain of youth out of the realm of mythology and into thelaboratory and ultimately, the clinic, the clues to this endeavour beingprovided by some of the lowliest (and annoying) organisms on earth. The secondlesson is just how committed the medical (and possibly political)establishments are to preventing this from happening and lastly, how deeplythe tentacles of vested interests (both personal and institutional) penetratethe hearts and minds of many doctors, administrators and medical educators andfunction to beat down any type of non conformist creativity which challengesthe status quo.THE EARLY YEARS I live in the Midwestern United States where I also grew upand received my education. I currently possess a Bachelor of Science, majoringin biology, and hold a master's degree in political science/internationaltrade. While my classmates in high school were attending ball games and doingwhat other high schoolers do, I was performing synthetic organic chemistry ina makeshift lab in my home. Developing novel non toxic agricultural chemicalsfor the control of pests was my initial preoccupation. Later I becameinterested in creating non toxic modalities for the treatment of cancer. Theseinterests were shaped by an unconventional junior high school biology teacherwho encouraged in vivo experimentation (apologies to anti vivisectionistreaders) and pressed students to do independent research to solve medicalproblems.It was during my high school years that I entered and won virtually everyscience fair with the various projects that I was undertaking. During mysenior year, I won first place in my state science fair and received the statemedical association's certification of distinction for designing novel classesof antineoplastics (anti cancer drugs). I was published professionally,received the American Chemical Society Award, my city's Engineering andScientific Society award and was inducted into my state's Academy of Scienceas well as into the New York Academy of Sciences and the American Associationfor the Advancement of Science before graduating from high school.In college I continued in my pursuits to unravel the mysteries of how cancercells develop and metastasise. As it was unusual for undergraduate students todevelop and run their own projects, I was fortunate to work with facultymembers in my biology and chemistry departments who gave me free run of theirfacilities. This research led to the development of new classes of compoundswhich could almost completely block invasion (the process by which cancercells migrate into healthy tissue). These compounds were essentiallynon toxic. I obtained funding for this research through a local oncologist andhis hospital, as well as from my university's foundation. My research wasfeatured on local television and in newspapers and I received severalaccolades, including the Who's Who Among Students in American Universities andColleges Award. Thus, upon receiving my bachelor's degree I had every reasonto suspect a successful passage through medical school and a productive careerin medical research.Upon entering medical school, I again had the fortune of working with afaculty member who understood the potential of my work and gave me anyassistance that he could render. I was funded by my oncologist acquaintance aswell as through grant money from the American Cancer Society and othergovernment funded organisations. I became steadily more engrossed in themysteries of the cell growth cycle and continued synthesising novel classes ofcell growth regulators that eventually led me to develop an entirely newperspective on such issues as the human life span, cancer and other illnessesthat my medical school professors were presenting as unrelated phenomena. Inow present this work in an abbreviated form to facilitate understanding byreaders without biomedical backgrounds.UNRAVELLING THE MYSTERIES OF THE AGES Although the stages of the cell growthcycle and the cellular and histological transformations that accompany themare fairly well known to medical science, the biochemical mechanisms thatbring these changes about are poorly defined at best. This is why currenttherapies for disease states which entail rapid and uncontrolled cell division(such as cancer), consist mainly of poisoning the offending cells with toxicdrugs (chemotherapy), radiation (radiotherapy), or removing them throughsurgery. Our understanding of the underlying mechanisms for the ageing processleaves even more to be desired. We have virtually no therapies today that caneffectively halt or even slow the vaunted biological clock. All we can hope todo is to cover up the signs of ageing through various cosmetic modalities andto treat various age related maladies (arteriosclerosis, heart disease, etc.,)with therapeutic regimens which address symptoms rather than ultimate causes.To anyone who has had to care for patients afflicted with the debilitatingsequelae of ageing or the horrendous consequences of life threatening cancers,this is a wholly unsatisfactory state of affairs that cries out for newinsights and approaches. Anyone who identifies the precise factors thatregulate what cells do at specific points in the cell growth cycle will haveachieved a quantum leap in our understanding not only of the genesis of cancerbut also of the age old question concerning why animals, including humans, ageand ultimately die. Such knowledge will not only enable medical science tosafely and effectively treat many disease states which today remain enigmatic,but also has profound ramifications for the cosmetic industry.CURRENT STATE OF LONGEVITY RESEARCH In order to overcome the limitations ofcurrent orthodoxies regarding cell growth and differentiation, it is necessaryto briefly review what those orthodoxies are. Within the appropriate body ofscholarship dealing with these issues, there have been two basic schools ofthought as to what causes cell senescence, cell death and the dysfunctionsassociated with neoplastic disease (e.g. cancer). The currently dominant oneis the free radical approach.Reduced to its most basic form, this view holds that cellular dysfunctions,which lead to cancer as well as ageing and eventual cell death, are caused bythe destructive action of environmental free radicals upon various importantcellular components such as DNA. In this fatalistic view, ageing can beunderstood as an irreversible and inevitable accumulation of cellular damage.It is my belief that this view is at least partially wrong.I was once told that research into prolonging the human life span was futilebecause "every living thing has to grow old and die". Yet, this fatalisticgeneralisation is patently untrue. Many unicellular organisms are effectivelyimmortal and reproduce by dividing indefinitely, only succumbing toenvironmental catastrophes, such as the Clorox bleach in your washingmachine.Likewise, there are multicellular organisms for which the concept of growingold is meaningless. Giant sequoia trees can be thousands of yearsold, yet keep on growing and producing vigorous and functional leaves andinternal structures such as xylem and phloem year after year, beingfelled only by lightning strikes or chain saws. Certain crustaceans such aslobsters grow bigger but do not manifest the age related declines in reflexesand physiological parameters that plague humans and other animals.Entomologists have long known that hormonal manipulation can preventmetamorphosis and keep insects in the juvenile state indefinitely. Thisknowledge has formed the basis for insecticide design.Likewise, hormonal cues control the development of plants by affecting theproliferation and differentiation of plant cells. Auxin class herbicides, suchas the ubiquitous 2,4-dichlorophenoxyacetic acid (2,4-D) have been used foreradicating dandelions from lawns for decades. These substances causediscordant cell growth and differentiation which leads to fatal morphologicalchanges and physiological dysfunctions. Considering how important suchhormonal systems are to the survival of such a diverse group of organisms, Ireasoned that mammals possess systems (even if in a vestigial state) which arefunctionally analogous, even if the specific chemistry may differ.A second approach to understanding ageing holds that cell growth,differentiation, ageing and death are not the sole result of accumulatedcellular damage or of some unstoppable biological clock which residesexclusively within cells, but that these are instead hormonally mediatedphenomena which result from the interaction of a cell's genes with chemicalsubstances present in the extracellular matrix and produced in remotelocations in the body.This theory is supported by various lines of converging evidence, includingresearch done on the rare disease progeria, a syndrome in which variousendocrine glands malfunction and the victim rapidly ages and usually diesbefore the chronological age of twenty. This devastating and poorly understooddisease strongly indicates that the biological clock can be reset andspeeded up, and that this speeding up is associated with the failure of thepineal gland (a pea sized gland which lies at the centre of the brain), aswell as the entire hypothalamic pituitary axis. The failure of these glands tosecrete vital hormones then causes the degenerative changes throughout thebody commonly associated with ageing, only much sooner than in healthyindividuals who lack the particular genetic defects associated with progeria.My own research, both in the library and the laboratory, has led me togradually put such observations together with findings from other lines ofinvestigation. For instance, it is now acknowledged that the hormonemelatonin, secreted by the pineal gland, plays a role not only inthe regulation of the sleep wake cycle, but also in prolonging life span andin some cases, halting and even reversing some of the symptoms of ageing inlaboratory animals and humans. The hormone also has anti cancer activity. Suchresearch, mostly performed in Europe, is amply cited in Dr. Walter Pierpaoli's1995 bestseller The Melatonin Miracle, and need not be dealt with in depthhere.1Since melatonin is already a commonly sold health supplement, it cannot bepatented by pharmaceutical companies and consequently has marshalled littleinterest from the medical establishment, at least on this side of theAtlantic. However, this is irrelevant from the perspective of my own.I believe that melatonin is an important, but relatively small piece of theoverall puzzle and my work has taken this line of research beyond Dr.Pierpaoli's discoveries into wholly uncharted territory.Synthesising this diverse basic research with the results of my own work incell culture and in vivo, I have formulated the following general conclusions:1. Melatonin's anti ageing and anti cancer effects are at least in part due tothe fact that this hormone, after it leaves the pineal gland (where it ismade), travels to the thymus gland located behind the breastbone and possiblyother endocrine glands where it functions as a "releasing hormone" andmodulates the synthesis of at least two other chemically distinct hormonesunacknowledged by medical science which I will label only as hormone "X" andhormone "Y" for our purposes here. I have identified the chemical structuresof these substances.2. It is both the relative and absolute ambient levels of hormones X and Y inthe body that modulate cellular growth, ageing and differentiation phenomena.This effect is in turn probably modulated by melatonin and at least one tracemetal or its organometallic complexes. Preliminary indications are that theseinteractions are complex and remain largely unknown due to the limitations infunds and facilities under which my previous work has been carried out. Theproduction of these substances is probably governed by complex feedback loopsthat involve the sex hormones, thyroid hormones, etc.. Elucidating theserelationships must remain one goal for future research.3. The thymus gland begins the process of involution after the chronologicalage of 20-30 years in humans. The pineal also calcifies and deteriorates. Thatis why CT and NMR scans of the heads of older individuals reveal a whitepea sized object in the basal area of the brain which I have seen many peoplemistake for alien implants. I submit that the deterioration of these glandsprecipitates a deflection in the concentrations of hormone X, hormone Y, orboth. The magnitude and direction (up or down) of these deflections isunknown, but is probably downward.4. It is this perturbation in the levels of hormones X and/or Y that triggerscell senescence and eventual death, causing tissues to stop turning over andprecipitating the physical declines associated with ageing. Since one of thesehormones is involved in maintaining cells in a differentiated state, thiscould provide the long awaited answer as to why cancer prevalence in generalincreases as we age, and also why sexual differentiation and other tissuedifferentiation declines in the same interval.5. Seemingly intractable problems can only be solved by reinterpreting theproblems in novel ways. Cancer cells can be thought of as normal cells whichhave reverted to a de-differentiated state, i.e. they resemble rapidlydividing, undifferentiated embryonic cells rather than the mature, slowlydividing, properly behaving normal cells of the tissues from which theyderive. It is also known to researchers that cancer cells are effectivelyimmortal; if given a proper environment, they can live and reproduceindefinitely, just as can bacteria and certain types of plant and fungalcells. This finding alone indicates that ageing and death are not theinevitable fates that they are made out to be, but are instead the results ofa program which can be altered. Although little has been made of this byconventional researchers, it strongly suggests that cancer is not a diseasestate, but a developmental problem, just as is ageing. Cancer cells are notbehaving badly, they are just behaving in a manner inappropriate for theirage. It is, in other words, a problem with the biological clock. Sincemelatonin is one of the substances that modulates the biological clock, thiswould explain melatonin's anti cancer effects and also suggested to me thathormones X and Y might have similar effects.6. Since the chemical structures of both hormones X and Y are attainable bytraditional means of organic synthesis, their manufacture is relativelystraightforward. As is also the case with many other currently acknowledgedhormones such as the oestrogens and progestins, it is possible to synthesiserelatively low molecular weight analogues of hormones X and Y which retain theparent molecule's biological activity. I have prepared several analogues ofthis type. These compounds show the same cellgrowth altering abilities of theparent molecules although the resources available to me did not facilitate thekind of evaluation necessary to reach detailed conclusions of the preciseactions of these compounds.7. I have developed other compounds whose chemical structure is quitedifferent from that of either hormones X or Y that seem to have similareffects on cancer cells.8. The exact mechanism of action of these compounds must at this point remainan object of speculation, since I did not possess the funds or the facilitiesto properly investigate this issue. Based on the chemical structure of thecompounds, however, it is reasonable to assume that, on a cellular level, theyact in a manner similar to that of steroid hormones and retinoids (such asvitamin A). This means that they probably penetrate the cell membrane and arethen translocated to the nucleus where they either promote or inhibit theexpression of genes which regulate the cell growth cycle. This is a much moresophisticated approach and stands in total contradistinction to the mode ofaction of virtually all existing anti cancer drugs which are really littlemore than cellular poisons designed to kill off all rapidly dividing cells.Such a shotgun approach is responsible for the sometimes horrendous sideeffects associated with conventional chemotherapy.The compounds that I have developed have obvious application in the non toxictherapy of cancer and other neoplastic diseases. They also threaten to givemedical science completely new insights into the interaction of the ageingprocess with various disease states. If the elatonin, hormone X,hormone Y axis is indeed responsible for regulating what cells do atparticular stages in their life cycle, then we can explain why, for instance,certain cancers tend to occur at particular points in people's lives. As weage, perturbations in the levels of hormones X and Y occur. The hypothesiswould predict the incidence of cancer to vary over the span of a person's lifeas well. Indeed, that is precisely what we observe clinically. As we age, theincidence of various cancers increases. This may be due to the fact that thelevels of hormones X and/or Y are no longer sufficient to maintain certaincells in a differentiated state, or that the immune system, whose own cellsdepend on specific amounts of X and Y, can no longer perform their function ofeliminating cancer cells properly.Finally, although it is too early to be talking seriously about a fountain ofyouth, I believe that hormones X and Y represent the first steps towardunravelling the mystery of why certain organisms and tissues age. Unlikemelatonin, the compounds that I have synthesised represent the firstpatentable drugs that actually have the potential of reversing or at leastslowing the much dreaded biological clock. They are the first non steroidal,non proteinaceous, non retinoid hormonally active substances other thanmelatonin and thyroid hormone known to affect cell growth and differentiationin higher animals. Furthermore, I have discovered that analogues of bothhormones X and Y exist in nature and can be prepared, for example, fromcertain plants. These substances can be incorporated into over the counterproducts such as cosmetics and vitamin preparations without the difficulty ofsurmounting regulatory hurdles. The impact, for instance, of a wrinkle creamwhich actually thickens the skin and returns cell turnover rates to levelsfound in a twenty year old should be obvious, especially since today'scosmetic preparations are mainly designed to cover up the effects of ageing.This leads me to question whether ancient legends of fantastic life span forhumans may not have a basis in reality. For example, thousands of years priorto the biblical era, a Sumerian legend relates the tale of a hero type figureby the name of Gilgamesh who travelled far and wide in his quest for eternallife. He finally found a plant growing under water that was able to bestow theimmortality that Gilgamesh sought. As the tale goes, however, instead ofconsuming the plant, he fell asleep. During his slumber, a snake ate theplant, hence the mythological explanation for snakes constantly sheddingand renewing their skin. The moral lesson of the story is, I suppose, "yousnooze, you lose". Due to Gilgamesh's carelessness, humankind was denied thesecret of eternal life.2 Alas, mythological descriptions of the "plant", ifthat is what it was, are not sufficient to make a positive identification.MEDICAL SCHOOL REALPOLITIK One would have thought that a student capable ofdoing research such as this would be a cause for great enthusiasm at anymedical school. My faculty advisor described me as "the most motivated studenthe has ever had." Alas, however, I would soon learn that there wereindividuals who considered me a threat rather than a prodigy, and I was soonto be plunged into a confrontation with forces that, at the time, I could notcomprehend.Between my first and second year of medical school, I was summoned to theoffice of a school administration official. Conversation quickly turned to myresearch. This raised my interest, as this official's duties did not includeoversight of student research programs. He declined to answer when I asked theidentity of the person that had informed him of my work. He asked why I haddecided to create my own research project rather than simply signing on to oneof the many existing projects offered by faculty members. This was, in hiswords "what most students did". I answered that I was not "most" students andthat I had entered medicine because I wanted to find new solutions to problemsthat conventional research had failed to find. Rather than eliciting praiseand encouragement, my answer only seemed to make him impatient and agitated.He enquired as to what was wrong with the available research projects. Iresponded that they were mundane and too limited by conventional paradigms toyield anything of importance in our battle with disease. I now went on theoffensive and asked what was wrong with my research, especially in light ofthe fact that I was bringing money and positive publicity to the school. Hereplied that "of course there was nothing wrong", and this concluded ourmeeting. I could not help but be left with the impression that this officialdid not accomplish his aims. My inquiries to other students revealed that noone else had undergone such an experience.This encounter was a turning point in my sojourn through medical school andthe subsequent campaign of behind the scenes persecution and harassmentlevelled against me, left me thinking that someone was taking lessons from theMalleus Maleficarum.One day I was summoned to the dean's office and told that there was "somethingwrong" with my performance in a particular class. Since my grades had beengood in this class up till that point, I was taken aback. I asked the dean totell me precisely what I was doing wrong and who had made the criticism. Ialso asked why the person making the complaint had taken it to the deaninstead of addressing me directly as per school protocol. He refused to answerand became agitated. I replied that if indeed I was doing something wrong Ihad the right to know the precise nature of the complaint as well as theidentity of the person making it. The dean's reply was that I had no suchright because his office was not a courtroom. This was to become a fairlystandard line of defence for the medical school administration.Despite my initial good grades and evaluations, the situation deteriorated asI progressed through clinical clerkships. Despite the fact that my performanceoutshone that of many other students, I found myself receiving negativeevaluations. Many of these evaluations were from individuals that I neverserved under, and hence, were pure fabrication. On other evaluation forms, thesignature of the evaluator was either absent altogether or was so illegiblethat even the clerkship coordinator claimed not to know who the person was.This was an obvious attempt to shield the individual from litigation.Protesting this kind of outright fraud to medical school administration fellon deaf ears, and only resulted in new criticism charging that I was being"defensive". In classic witch hunt fashion, any attempts by me to show thatthe charges against me were false were only reinterpreted as additionalevidence of my guilt or even psychopathology. I was referred to a psychologistand put through a battery of personality inventories. When these came backnormal, the school administration simply ignored the results and proceeded tomake me jump through an infinite series of new hoops in order to make meappreciate my status as persona non grata. This treatment finally resulted inmy leaving medical school partway through my third year. My antagonistsrealised that I could not afford legal aid and thus felt secure that theirmachinations could not be effectively countered.Other more mysterious goings on seemed to swirl around my research while atmedical school. One faculty member refused to address me in the halls and madea point of walking out during conferences when I presented my research. Onmore than one occasion, I entered my lab to find that my possessions had beensearched. To top things off, I received phone calls from someone claiming tobe my friend. This person informed me that things would "only get worse" forme at medical school unless I "stopped playing God". He refused to give hisname or to explain precisely what he meant by his admonition. As one canimagine, my leaving medical school was like lifting a huge weight from myshoulders, despite the fact that I had to discontinue my research. Theoncologist that I had worked with later perished ostensibly of a heart attackwhile on vacation. Since I cannot show that this was anything but a naturaloccurrence, I leave it to the reader to decide. After his death, the hospitalwhere he was employed no longer funded my project citing "other priorities".When all is said and done, what are we to make of all this? Was I the targetof industrial espionage? If so, they got nothing, as I have always made apoint of carrying my lab notebooks with me at all times and even my facultyadvisor was not made privy to the chemical formulas of the compounds that Iwas developing.Was this something entirely different? Was it an attempt to simply quash myresearch? If so, did this involve only officials at the medical school or didit go higher? What could have evoked such a concerted hate campaign against,of all people, a lowly medical student? Did "they" know something about thedirection and ramifications of my research that even I did not know at thetime?Given the vitriol directed against me, I cannot help but think that I am onthe right track to something. I suppose that I should thank mytormentors for inadvertently confirming what they did not let me have time toconfirm in the lab. If the goal of the powers that be was to marginalise me,then they have succeeded, at least for the time being. I am unemployableand my life has been reduced to financial ruin. I have pursued education inother fields. I am currently attempting to pursue my research privately sinceit remains patentable. I have made arrangements that all proprietary detailsof the research be made public in the event of my untimely demise, although Ibelieve that my tormentors have been quite happy keeping me jobless andimpoverished.Since becoming an avid NEXUS reader a couple of years ago, I have interpretedmy plight in a different light and have begun to ask questions that wouldnever have occurred to me in medical school. Up until recently, I haveoperated under the naïve premise that the purpose of the health care industrywas to eliminate disease and promote human well being. NEXUS readers knowbetter. I leave readers with the following questions and welcome feedback:What would the implications be for the health care juggernaut if mostillnesses associated with advancing age could be eliminated by having everyonetake one pill daily? What would happen to our beleaguered social securitysystem if the human life span could be doubled? What would be the impact onorganised religion if one of the two certainties of life, i.e. death, was nolonger a certainty?About the Author: Andrew Sokar is a biologist who lives in the Midwestern US.He has a Bachelor of Science, majoring in biology and a master's degree inpolitical science with a specialisation in internatinal trade, for which hegraduated with high distinction. He continues to pursue his researchindependently, especially into the over the counter applications for hisrejuvenation technology. He welcomes correspondence at:slowsubversion.Endnotes:1. Walter Pierpaoli, William Regelson and Carol Colman, 1995, The MelatoninMiracle, Pocket Books, New York. See also William Regelson and Carol Colman,1996, The Superhormone Promise, Pocket Books, New York2. N.K. Sanders, 1972, The Epic of Gilgamesh, Penguin, London.-----------Extracted from Nexus Magazine, Volume 12, Number 4 (June - July 2005)http://www.nexusmagazine.com/backissues/1204.conts.htmlPO Box 30, Mapleton Qld 4560 Australia. editorTelephone: +61 (0)7 5442 9280; Fax: +61 (0)7 5442 9381Taken rom our web page at: http://www.nexusmagazine.com