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The U.S. Transhumanist Party’s First 1,000 Members: An Aggregate Demographic Analysis

The U.S. Transhumanist Party’s First 1,000 Members: An Aggregate Demographic Analysis

Gennady Stolyarov II


On July 7, 2018, the United States Transhumanist Party finally reached its major milestone of 1,000 members.  The U.S. Transhumanist Party collects extremely limited information on its members as a way of respecting their privacy; generally, we only request enough information to be able to contact our members and identify where (in terms of general jurisdiction) they are located. However, it is still possible to derive some general, aggregated insights from overall membership data without compromising any individual member’s privacy. The U.S. Transhumanist Party makes such aggregated data available for the purposes of providing insights as to the composition of the largest transhumanist political organization in the world, which may indirectly (though not precisely) shed insights into the composition of the broader transhumanist movement – at least in terms of identifying where transhumanists tend to be concentrated and areas where the movement is making inroads, as well as continued challenges in reaching certain areas and demographics. Caution should be exercised, however, in considering this information to be “set in stone”, as it is merely a snapshot in time of membership composition, which itself will evolve as new members are added. Furthermore, it is possible that the proportion of individuals who have thoughts or sympathies that could be broadly construed as transhumanist would differ from the proportion of members of the U.S. Transhumanist Party – even based on incidental elements such as the current reach of the U.S. Transhumanist Party’s social networks and media presence, which may be uneven across various constituencies, but which we are always striving to improve.

Members by Type (United States or Allied)

United States Members (Eligible to vote in U.S.): 704 – 70.4%
Allied Members (Anyone else capable of holding a political opinion): 296 – 29.6%

Commentary: As was anticipated by U.S. Transhumanist Party leadership prior to this analysis, approximately 70% (70.4%) of members are eligible to vote in U.S. elections, and those members largely reside in the United States, while 30% (29.6%) of members are Allied Members – either U.S. residents who are not eligible to vote in U.S. elections, or transhumanists residing in other countries. All members, including Allied Members, are eligible to take part in the internal votes and deliberations of the U.S. Transhumanist Party, as we pride ourselves on our cosmopolitan, international character and see the future of humankind as gradually rendering national distinctions ever less relevant, since the transformative impact of technological progress transcends all national and ethnic boundaries and will hopefully benefit all humankind to the maximal extent possible.

The U.S. Transhumanist Party began to collect information about members’ specific jurisdictions in December 2017. This information was supplemented in the present analysis by additional information known directly to U.S. Transhumanist Party leadership regarding particular members’ jurisdictions of residence. As a result, 437 out of 1,000 members were able to be matched with a particular jurisdiction of residence, which is at presently utilized for aggregate data-analysis purposes only. The U.S. Transhumanist Party does not collect more granular residence information about its members, other than their U.S. state or non-U.S. country of residence.

Members by U.S. State
(Only members who identified their state or otherwise were known to reside there were tabulated.)

Non-U.S. Members by Country
(Only members who identified their country of residence or otherwise were known to reside there were tabulated.)

Commentary: The plurality of United States Members of the U.S. Transhumanist Party reside in California, while other states of prominent member presence include New York, Florida, Arizona, Ohio, Texas, Colorado, and Washington. This is not surprising, given the concentration of technologically oriented businesses in California, as well as the high population numbers in many of the other listed states. Colorado, Nevada, and Oregon, however, appear to have higher concentrations of Transhumanist Party members relative to their populations. Allied Members have a widespread international presence and representation on almost all continents. Among non-U.S. members, the largest numbers appear to be in the United Kingdom and Canada – where transhumanists often closely interact with their counterparts in the United States – as well as India, where we attribute the prominent member presence to interest in technology, a rapidly changing society and economy, strong ties with the West through immigration and educational exchange, as well as the fact that India is now the world’s second-most populous country.  Unfortunately, the world’s most populous country, China, is only represented by one member (who recently immigrated there). We attribute this to the lack of political freedom in China and the restrictions on information access imposed by the Chinese government. While the Chinese government has numerous favorable attributes – including a pragmatic, pro-economic-growth, generally pro-technology outlook, the unfortunate inclination toward authoritarian control of the social and political spheres prevents what would have been many otherwise highly beneficial collaborations between the U.S. Transhumanist Party and residents of China.

Members by Gender

Commentary: The U.S. Transhumanist Party does not directly inquire about any member’s gender – nor does the U.S. Transhumanist Party take any position on gender issues, the origin of gender, post-genderism, or related matters – other than to affirm its commitment to inclusivity and openness to all individuals who share our Core Ideals, irrespective of their gender, gender identity or expression or lack thereof, or specific views on gender issues. However, an aggregate analysis of member composition by gender may be informative as to the extent to which the U.S. Transhumanist Party could continue to expand its reach and the effectiveness of its message.

For most members, it was possible to discern their gender by considering their names – since names are most often gender-specific – or, if the members happened to be personally known to leadership of the U.S. Transhumanist Party, this information was also utilized to accurately determine those members’ genders. For some members such a determination was not possible based on the information provided, so they were classified as “Unknown” for purposes of this analysis. This is a sufficiently small category that it was grouped with those members who are known to specifically identify as agender or non-gender.  The U.S. Transhumanist Party does not guarantee the complete accuracy of this analysis, but we are reasonably confident that at least 95% of the members’ gender was identified accurately. Based on this confidence, we can also posit that the material conclusions of the analysis would not be affected if additional or revised information about a small number of members’ gender were made available.

Male Members: 854 – 85.4%
Female Members: 133 – 13.3%
Agender Members and Members of Unknown Gender: 13 – 1.3%

There is nothing gender-specific about transhumanism, and the aspirations and values of transhumanism are aimed at benefiting all humans and other sentient entities – so, at first glance, it is rather difficult to understand why a significant apparent proportional difference by gender exists in U.S. Transhumanist Party membership counts. There is no single definitive hypothesis as to why this is presently the case. However, the existence of this difference was anecdotally known to U.S. Transhumanist Party leadership prior to this analysis, and a heuristic figure of 80% male / 20% female composition for the transhumanist movement as a whole was used in communications on this issue. It is noteworthy that, while the actual proportions are possibly closer to 86% male  /14% female, the composition of newer members (those who signed up in 2018) has been 83.4% male / 15.2% female / 1.3% unknown, so it is possible that proportionally more individuals who identify as female are becoming aware of and interested in transhumanist ideas and the work of the U.S. Transhumanist Party. Furthermore, many female members of the U.S. Transhumanist Party are prominent public figures whose work appears regularly on our website and whose contributions to the actualization of our goals are highly valued.

One possibility is that the initial gender difference in U.S. Transhumanist Party membership composition is an artifact of a similar gender difference in the “tech” industry, with which many (though not all) transhumanists happen to have some association. Any gender disparities in the “tech” industry existed prior to the emergence of transhumanism and arose completely independently of transhumanism or transhumanist projects or activism. It may simply be the case that individuals in the “tech” industry are more likely to be aware of transhumanism and developments in Transhumanist politics in the first place, and it takes additional work to reach constituencies outside of the “tech” industry. Fortunately, if this interpretation is accurate, then the U.S. Transhumanist Party is one of the best available vehicles for undertaking this task, since its leadership is predominantly not culturally or organizationally tied to large technology companies or the norms of Silicon Valley, but rather tends to be substantially more diverse and independent in terms of backgrounds, skill sets, and outlooks.

Ultimately, we seek to grow our membership everywhere and work toward an entire world which identifies as transhumanist. With this, we encourage everyone, of all genders, countries, backgrounds, and skill sets, to sign up for absolutely free membership in the U.S. Transhumanist Party and begin to contribute to the progress of our mission to put science, health, and technology  at the forefront of politics and thereby create a world of indefinitely long life, universal abundance, rational and policy-oriented politics, and protection against all existential risks. The composition of our membership going forward can be affected by you.

Proposal for Chimeric Gene Therapy (v1.3.1) – Curing Trauma, Addiction, and Conditioning – Paper by Kyrtin Atreides

Proposal for Chimeric Gene Therapy (v1.3.1) – Curing Trauma, Addiction, and Conditioning – Paper by Kyrtin Atreides

Kyrtin Atreides


Editor’s Note: The U.S. Transhumanist Party has published this research paper and proposal for a practical gene therapy by member Kyrtin Atreides in order to solicit input from other researchers in the field of gene therapy as well as to provide some ideas for further directions in research and practical applications of genetic engineering. The U.S. Transhumanist Party does not itself conduct research or recommend particular medical procedures, so the publication of this paper should be seen as promoting the exploration of research paths that could one day (hopefully sooner rather than later) materialize into viable treatments for curing diseases and lengthening lifespans. 

~ Gennady Stolyarov II, Chairman, United States Transhumanist Party, April 1, 2018

Introduction:

A wise medical director once told me that 50% of those who go into the field of Psychology need psychological help themselves. I suspect that one day I’ll be able to say the same of genetic engineering.

Epigenetics control our neurochemistry, which dictates base level reactions to stimuli, and everything from a bad meal, job, relationship, or traumatic childhood event, to warzone PTSD, can trigger epigenetic changes. [1] De Bellis, M. D., & A.B., A. Z. (2014), [2] Gudsnuk, K., & Champagne, F. A. (2012), [3] Hardy, T. M., & Tollefsbol, T. O. (2011)

Over time these changes build up, and since human society is often highly unstable due to rapid and lopsided progression, the net result is cumulative damage, similar to aging, because epigenetics attempt to attune you to an environment that doesn’t change in compatible ways. [4] Bowers, E. C., & McCullough, S. D. (2017)

What this means is that in order to roll back the clock the epigenetic equation needs to be recalculated in a local space, a process which occurs with a viral knockout, or insertion of new genetic data, within a region surrounding any given gene. The basic idea is that if you alter the dimensions of the space that the epigenetic equation covers via methylation, you cause it to recalculate the ideal distribution and genetic activation for that region based on current data, rather than the trauma which previously altered it.

By causing this update to take place, the gene expression is recalculated to values which are more closely aligned with current needs and environmental factors. Previously in human history, lives were shorter and epigenetic influences served a healthy role in promoting survival, but the problem with amassing a large pile of trauma-induced epigenetic changes becomes acutely apparent as age increases.  [5] Teschendorff, A. E., West, J., & Beck, S. (2013)

Each change is based on data fixed to the point of trauma, and any alteration to that expression is glacially slow, if it occurs at all. Often times such changes break an element of neurochemistry in the sense that the change can’t naturally reverse itself once it has been made, but it can be easily reversed with minor engineering.

Different genes act like functions in code, separate blocks which can function together, but which also contain sites where new code can be placed without causing harm to the current code. In the same way the human genome also contains 8% integrated viral DNA, which makes for an ideal target for gene knock-out.  [6] (International Human Genome Sequencing Consortium, 2001; Smit, 1999)

Proposal Part 1:

What I propose is two-fold. The first step is the creation of a gene therapy which is practically viable, costing no more than $5 per person in production. The second step is testing the top gene sites active in controlling neurochemistry with both knock-out of viral DNA, and knock-in of dormant placeholder DNA, to cause recalculation to take place.

The first is easily accomplished by understanding the nature of why anything evolves in the first place, for survival. If you create a gene therapy whose survival is guaranteed it loses reason to adapt maliciously, because there is no advantage to be gained. A classic case that demonstrates a virus becoming less lethal over time is HIV, where initially it was a death sentence, but over time not only were treatments developed, the virus became less lethal, because that lethality was acting as a detriment to the purpose of survival, and it evolved in order to live longer. [7] Payne, R., Muenchhoff, M., Mann, J., Roberts, H. E., Matthews, P., Adland, E., … Goulder, P. J. R. (2014)

The myriad of bacteria, archaea, viruses, and eukaryotic microbes in our bodies that outnumber our own cells have come to a balanced state, where our bodies are the ecosystem, and as that 8% viral DNA demonstrates a virus is no different, it favors survival and a stable environment. [8] Eloe-Fadrosh, E. A., & Rasko, D. A. (2013)

I mention this because of a key factor which makes gene therapy completely impractical today, 293T cells. Having to use specialty cells for cloning a virus that isn’t replication-competent, and is often very fragile to begin with, is one monumental waste, which is built on the unfounded fear that a replication-competent virus is in and of itself a threat. As machine learning is applied to the human genome, as well as non-human genomes, the error in that line of reasoning will become increasingly apparent.

What we need is a new gene therapy, engineered for high conversion rates, such as Adeno-Associated-Virus-7 or Lentivirus, and hybridized with a more durable, low-symptom (“clinically silent”), low-transmission-potential virus, such as Epstein-Barr Virus. By making such a virus replication-competent, but also self-inactivating (EBV) and able to integrate itself as a genetic landing site capable of being periodically updated, not only is the problem of practicality and cost solved, but the speed with which new research can be tested is greatly accelerated, and the virus is rendered stable. EBV in particular is already present in roughly 95% of adults, as it has integrated with their genomes. When combined with revised best practices any risk of bad-actor genetic engineering remains a practical impossibility.

By keeping the intermediate stages of the gene therapy in a controlled environment and only releasing the end result beyond that point, the Bio-Safety risk remains functionally unchanged, as the hypothetical “bad actor” would still require the same advanced tools, knowledge, and materials to generate a harmful virus as they already do today. The key difference in Bio-Safety terms is that by allowing the field to advance, the benefits and possible means of defense against that hypothetical would move forward, while undermining the root cause of said hypotheticals. This would be roughly equivalent to creating bulletproof sleepwear before the invention of the firearm.

The end result of utilizing such a gene therapy would be a symbiotic relationship with a genetic update mechanism, where increases to lifespan and survival rates favor both parties, resulting in potential rare mutations that better serve that purpose, like a bird evolving a better beak for catching fish.

Selection of EBV to hybridize with Lentivirus would also allow for the therapy to enter dormant cycles, avoiding immune-system rejection, and reactivating when introduced to engineered updates from additional gene therapy treatments. [9] Houldcroft, C. J., & Kellam, P. (2015)

The replication-competent gene therapy can be created with either AAV-7 or Lentivirus by means of recombination during the manufacturing process. An AAV-2 or AAV-7 variant may be preferable, if not required, for the treatment of HIV-positive humans due to the risk of interaction between any Lentivirus gene therapy and the HIV virus. It is however probable that a Lentivirus/EBV chimeric gene therapy would overwrite wild HIV virus variants rather than being overwritten by them, but rigorous testing is required, which development of this therapy would also make possible. This is partly due to the far greater size, complexity, and long-term stability of EBV compared to Lentivirus. [10] Haifeng Chen. (2015)

On a side note the genetics study that led me to realize this epigenetic mechanic was in play is shown here:

[11] Welle, S., Cardillo, A., Zanche, M., & Tawil, R. (2009)

It was by examining the difference between an adult with gene knock-out applied after maturation versus one born with the modification that the mechanic of Methylation Dimensions / Dimensions of DNA was illuminated. Since this process occurs naturally as a part of viral integration, a mechanic had to evolve that could handle the recalculation. The above study also highlights that gene therapies shouldn’t be administered to individuals prior to adulthood, due to the differences in how they impact an individual prior to biological maturation, unless the need is dire, or unless the difference can be corrected upon maturation.

Another failing point of gene therapies as they exist today is that, due to the lack of replication-competence, viral titers act as a choke-point, where the virus is injected in-mass rather than gradually converting cells, massively increasing the risk of cellular toxicity and immunotoxicity. If a gene therapy was replication-competent, even an extremely low dose could achieve a high level of cellular conversion over a period of time, potentially closing in on Bayes Error, regardless of host mass. In effect, the same dose that yields positive results in a mouse could also work for a human. [12] White, M., Whittaker, R., Gándara, C., & Stoll, E. A. (2017)

Proposal Part 2:

Once the new gene therapy is complete, the ability to repair damage at the epigenetic level becomes practical, speeding up the testing process by an order of magnitude, as well as greatly reducing cost.  For the purpose of initial testing and separation of documented effects, knock-out of viral DNA and placeholder-gene knock-in will be targeted to recalculate small regions surrounding key neurochemistry controlling genes, a few of which I’ve listed below:

HTR6 – Chromosome 1 – (5-Hydroxytryptamine Receptor 6) is a Protein Coding gene.  Diseases associated with HTR6 include Acute Stress Disorder and Amnestic Disorder.

NR4A2 – Chromosome 2 – (Nuclear Receptor Subfamily 4 Group A Member 2) is a Protein Coding gene. Diseases associated with NR4A2 include Arthritis and Late-Onset Parkinson Disease. Among its related pathways are Dopaminergic Neurogenesis and Corticotropin-releasing hormone signaling pathway. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding, and protein heterodimerization activity. An important paralog of this gene is NR4A3.

HES1 – Chromosome 3 – (Hes Family BHLH Transcription Factor 1) is a Protein Coding gene. Among its related pathways are Signaling by NOTCH1 and NOTCH2 Activation and Transmission of Signal to the Nucleus. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding, and sequence-specific DNA binding. An important paralog of this gene is HES4. [13] Epigen Global Research Consortium(2015)

DRD5 – Chromosome 4 – (Dopamine Receptor D5) is a Protein Coding gene.  This receptor is expressed in neurons in the limbic regions of the brain. It has a 10-fold higher affinity for dopamine than the D1 subtype.

SLC6A3 – Chromosome 5 – (Solute Carrier Family 6 Member 3) is a Protein Coding gene. Diseases associated with SLC6A3 include Parkinsonism-Dystonia, Infantile and Nicotine Dependence, Protection Against.

DRD1 – Chromosome 5 – (Dopamine Receptor D1) is a Protein Coding gene.  Diseases associated with DRD1 include Cerebral Meningioma and Drug Addiction.

TAAR1 – Chromosome 6 – (Trace Amine Associated Receptor 1) is a Protein Coding gene. Although some trace amines have clearly defined roles as neurotransmitters in invertebrates, the extent to which they function as true neurotransmitters in vertebrates has remained speculative. Trace amines are likely to be involved in a variety of physiological functions that have yet to be fully understood.

DDC – Chromosome 7 – (Dopa Decarboxylase) is a Protein Coding gene. Among its related pathways are Dopamine metabolism and Metabolism.

CRH – Chromosome 8 – CRH (Corticotropin Releasing Hormone, aka CRF) is a Protein Coding gene. Diseases associated with CRH include Crh-Related Related Nocturnal Frontal Lobe Epilepsy, Autosomal Dominant and Autosomal Dominant Nocturnal Frontal Lobe Epilepsy. Among its related pathways are G alpha (s) signalling events and Signaling by GPCR. GO annotations related to this gene include receptor binding and neuropeptide hormone activity. [14] Sandman CA, Curran MM, Davis EP, Glynn LM, Head K, Baram TZ.(2018)

HTR7 – Chromosome 10 – (5-Hydroxytryptamine Receptor 7) is a Protein Coding gene. Diseases associated with HTR7 include Autistic Disorder and Byssinosis.

ETS1 – Chromosome 11 – (ETS Proto-Oncogene 1, Transcription Factor) is a Protein Coding gene. Among its related pathways are Photodynamic therapy-induced NF-kB survival signaling and MAPK-Erk Pathway. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding and transcription factor binding. An important paralog of this gene is ETS2.

HTR2A – Chromosome 13 – (5-Hydroxytryptamine Receptor 2A) is a Protein Coding gene. Diseases associated with HTR2A include Schizophrenia and Major Depressive Disorder and Accelerated Response to Antidepressant Drug Treatment.

SLC6A4 – Chromosome 17 – (Solute Carrier Family 6 Member 4) is a Protein Coding gene. Diseases associated with SLC6A4 include Obsessive-Compulsive Disorder and Slc6a4-Related Altered Drug Metabolism.

TCF4 – Chromosome 18 – (Transcription Factor 4) is a Protein Coding gene. Among its related pathways are Mesodermal Commitment Pathway and Regulation of Wnt-mediated beta catenin signaling and target gene transcription. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding and protein heterodimerization activity. An important paralog of this gene is TCF12.

OXT – Chromosome 20 – (Oxytocin/Neurophysin I Prepropeptide) is a Protein Coding gene. This gene encodes a precursor protein that is processed to produce oxytocin and neurophysin I. Oxytocin is a posterior pituitary hormone which is synthesized as an inactive precursor in the hypothalamus along with its carrier protein neurophysin I. Together with neurophysin, it is packaged into neurosecretory vesicles and transported axonally to the nerve endings in the neurohypophysis, where it is either stored or secreted into the bloodstream. The precursor seems to be activated while it is being transported along the axon to the posterior pituitary. This hormone contracts smooth muscle during parturition and lactation. It is also involved in cognition, tolerance, adaptation, and complex sexual and maternal behavior, as well as in the regulation of water excretion and cardiovascular functions.

AVP – Chromosome 20 – (Arginine Vasopressin) is a Protein Coding gene. Diseases associated with AVP include Diabetes Insipidus, Neurohypophyseal and Hereditary Central Diabetes Insipidus. Among its related pathways are G alpha (s) signalling events and HIV Life Cycle. GO annotations related to this gene include protein kinase activity and signal transducer activity. An important paralog of this gene is OXT.

These genes represent only a fraction of the neurochemistry control sites, but they are disproportionately represented in terms of impact due to being frequently targeted by a wide variety of damaging sources focused on addiction, conditioning, reward-behaviors, and various forms of trauma.  By changing the dimensions of a region that methylation, phosphorylation, acetylation, and histone modification have to cover the recalculation is triggered and optimized to the current environment. [15] Tuesta, L. M., & Zhang, Y. (2014), [16] Samonte FGR.(2017)

It is also worth noting that in the case of more extreme imbalances two or more gene targets would either need to be iteratively, or simultaneously, recalculated in order to reach a balanced state. By using one gene therapy, then a second on the parallel site, such as the case with OXT vs. AVP balance, you could iteratively progress towards a balanced state with less extreme gene expression levels, like turning the sides of a Rubik’s Cube. Using multiple versions of the same gene therapy, attaching to different target sites, this process could be activated simultaneously, causing the recalculation to factor in all discovered and targeted regions at once, effectively “training” the epigenetic weights of highly connected regions, instead of working iteratively where half of them are frozen at any given time. Initially this simultaneous trigger could be via standard injection, but it could also be automated a variety of ways, including using links to circadian rhythm conditions and seasonal changes, causing routine recalculation of mental and emotional health critical gene expression. [17] Neumann, ID, Landgraf R.(2012)

Since none of the genes are directly impacted, only recalculating their level of activation, risk is kept to a bare minimum, and the same approach can be repeated to yield different results by varying the conditions present as the gene therapy takes effect.  Ideal circumstances for any given outcome can be established by varying environmental factors until the result is optimized, potentially even personalized, and though this approach would be ideally suited for a laboratory environment, it could also help to establish best-practices for administering the gene therapies once they reached human trials.

Results of epigenetic recalculation could be further utilized for mathematically modeling the potential space of gene activation when coupled with environmental data from the trial facility, increasing prediction accuracy for post-therapy gene expression, as well as the subsequent benefits.

The before-versus-after comparison between fully mapped genomes could also be used in Deep Neural Network terms to generate accurate predictions for post-therapy gene activation levels and the approximate benefits of those changes. A DNN could even be modeled to map causal relationships between epigenetic activation changes in a way that has likely never been done before, allowing for many genes with currently unknown functions to be defined, opening the door to more advanced models that could map the causal and probable space of genetic engineering with far greater accuracy.

In Closing:

How long we remain mired in the Medieval times of genetic engineering is purely up to us, as a collective we can form a safety committee which agrees to create a practical gene therapy that shifts the paradigm away from monopolistic control to one where science can advance, and people can benefit from advances without waiting 20 years for approval.

The best way to win the hearts and minds of people around the world is to give them something to be grateful for, benefiting either themselves or those they love in meaningful ways. I can think of no better start down this path than curing the epigenetic effects of trauma, as virtually everyone has suffered some form of trauma in their lives, and many are needlessly crippled by it today.

Without the scars left on humanity at the epigenetic level the negative-influence house of cards collapses, along with all of the industries who prey upon it, breaking the downward spiral and moving the dial forward, from pointing towards a deeper Dystopia to a brighter future.

Transhumanism is likewise about the freedom to choose who you are, and who you become, which in the field of genetic engineering means that a practical method for genetic updates is as much a prerequisite as the computer was a prerequisite for the Internet. It would by no means remove the threat of archaic legal constructs, but it would greatly reduce their potency, taking us one step closer to being truly Transhuman.

Taking this a step further, the ability to reset the epigenetic level influence of trauma, addiction, and conditioned behaviors is also prerequisite to any major social change, as backlash comes into play when friction of the old meets new paradigms. The act of curing the effects of trauma would in this way also serve to make people more open to new ideas, since the baseline of their neurochemistry shifting would trigger subsequent recalculation going up the chain, all the way to higher order cognitive functions. This could potentially be used to shift neurochemistry into unexplored probability space, allowing for configurations that couldn’t arise naturally.

Without the practical potential there is no room for innovation, and progress stagnates behind monumental pay-gates, but the solution can be engineered today, giving innovators access to build a better tomorrow.

Humanity is but one life form among billions of ever-evolving forms of life that we know of today, and even if only 1 in 10,000 of those lifeforms were evolving in ways compatible with our genetic structure we’d be wasting 99.9999% of the potential evolutionary improvements being made by other species.  Life in the known universe is in a perpetual race to evolve, and to compete in that race in any meaningful way, increasing the survival of the species, it is necessary to take advantage of the advances that other forms of life make, the other 99.9999%+ compute power dedicated to the task of evolving into ever more advanced and resilient beings.  While humanity may not be ready to take this step any time soon, perhaps once the world is cured of trauma this will enter the realm of consideration.

If humanity is to survive, let alone thrive, in the hazards of space, genetic engineering that grants us the resilience of life forms able to survive considerable exposure to radiation, extreme temperatures, increased gravity, and even the vacuum of space, are required for us to move forward. Even survival on Earth is a moving target, and as humanity stands today, vulnerability to any number of cataclysms remains much higher than it could be. Fans of longevity research should favor the generation of a practical gene therapy most of all, because it would only take a few direct gene edits using such a therapy to significantly increase life span, granting talented scientists more years with which they could work towards overcoming challenge after challenge.

Limiting gene therapy treatment to the rarest of diseases is like limiting internet access to the most remote parts of the world, an astronomical waste, and it is time for that to change. From the more directly Transhumanist perspective, this is a step towards being free to choose who you are right down to the genetic level, accessible to everyone, a basic human right that has yet to be written, but before reaching that point humanity needs an epigenetic tabula rasa, a slate clean of trauma, conditioning, and addiction.

Kyrtin Atreides is a researcher and member of the U.S. Transhumanist Party. In his spare time over the past two years, he has conducted research into Psychoacoustics, Quantum Physics, Genetics, Language (Advancement of), Deep Learning / Artificial General Intelligence (AGI), and a variety of other branching domains, and continues to push the limits of what can be created or discovered.

For additional reading on the subject matter mentioned herein, please refer to:

Lentivirus: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837622/

https://viralzone.expasy.org/264?outline=all_by_species

Adeno-Associated Virus: https://www.wjgnet.com/2220-3184/full/v5/i3/28.htm

https://microbewiki.kenyon.edu/index.php/Epstein-Barr_Virus

Formal Citations:

1. De Bellis, M. D., & A.B., A. Z. (2014). “The Biological Effects of Childhood Trauma.” Child and Adolescent Psychiatric Clinics of North America23(2), 185–222. http://doi.org/10.1016/j.chc.2014.01.002

2. Gudsnuk, K., & Champagne, F. A. (2012). Epigenetic Influence of Stress and the Social Environment. ILAR Journal53(3-4), 279–288. http://doi.org/10.1093/ilar.53.3-4.279

3. Hardy, T. M., & Tollefsbol, T. O. (2011). Epigenetic diet: impact on the epigenome and cancer. Epigenomics3(4), 503–518. http://doi.org/10.2217/epi.11.71

4. Bowers, E. C., & McCullough, S. D. (2017). Linking the Epigenome with Exposure Effects and Susceptibility: The Epigenetic Seed and Soil Model. Toxicological Sciences155(2), 302–314. http://doi.org/10.1093/toxsci/kfw215

5. Teschendorff, A. E., West, J., & Beck, S. (2013). Age-associated epigenetic drift: implications, and a case of epigenetic thrift? Human Molecular Genetics22(R1), R7–R15. http://doi.org/10.1093/hmg/ddt375

6. Pakorn Aiewsakun, Aris Katzourakis(2015) Endogenous viruses: Connecting recent and ancient viral evolution. Virology. 2015 May;479-480:26-37. doi: 10.1016/j.virol.2015.02.011. Epub 2015 Mar 12.

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Induced Cell Turnover: A Proposed Modality for In Situ Tissue Regeneration and Repair – Press Release by Biogerontology Research Foundation

Induced Cell Turnover: A Proposed Modality for In Situ Tissue Regeneration and Repair – Press Release by Biogerontology Research Foundation

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Biogerontology Research Foundation


Scientists at the Biogerontology Research FoundationFeinberg School of Medicine at Northwestern University and Swammerdam Institute of Life Sciences at the University of Amsterdam have published a paper on a proposed method of in situ tissue regeneration called Induced Cell Turnover (ICT) in the journal Human Gene Therapy. The proposed therapeutic modality would aim to coordinate the targeted ablation of endogenous cells with the administration of minimally-differentiated, hPSC-derived cells in a gradual and multi-phasic manner so as to extrinsically mediate the turnover and replacement of whole tissues and organs with stem-cell derived cells.

“One of the major hurdles limiting traditional cell therapies is low levels of engraftment and retention, which is caused in part by cells only being able to engraft at locations of existing cell loss, and by the fact that many of those vacancies have already become occupied by ECM and fibroblasts (i.e. scar tissue) by the time the cells are administered, long after the actual occurrence of cell loss. The crux underlying ICT is to coordinate endogenous cell ablation (i.e. induced apoptosis) with replacement cell administration so as to manually vacate niches for new cells to engraft, coordinating these two events in space and time so as to minimize the ability for sites of cell loss to become occupied by ECM and fibroblasts. This would be done in a gradual and multi-phasic manner so as to avoid acute tissue failure resulting from the transient absence of too many cells at any one time. While the notion of endogenous cell clearance prior to replacement cell administration has become routine for bone marrow transplants, it isn’t really on the horizon of researchers and clinicians working with solid tissues, and this is something we’d like to change,” said Franco Cortese, Deputy Director and Trustee of the Biogerontology Research Foundation, and lead author on the paper.

Cell-type and tissue-specific rates of induced turnover could be achieved using cell-type specific pro-apoptotic small molecule cocktails, peptide mimetics, and/or tissue-tropic AAV-delivered suicide genes driven by cell-type specific promoters. Because these sites of ablation would still be “fresh” when replacement cells are administered, the presumption is that the patterns of ablation will make administered cells more likely to engraft where they should, in freshly vacated niches where the signals promoting cell migration and engraftment are still active. By varying the dose of cell-type targeted ablative agents, cell type and tissue-specific rates of induced turnover could be achieved, allowing for the rate and spatial distribution of turnover to be tuned to the size of the tissue in order to avoid ablating too many cells at once and inadvertently inducing acute tissue failure.

“Cell therapies are limited by low levels of engraftment, and in principle their ability to improve clinical outcomes is limited by the fact that they can only engraft at locations of existing cell loss. Conversely, therapeutic tissue and organ engineering requires surgery, is more likely to introduce biochemical and mechanical abnormalities to tissue ultrastructure through the decellularization process, and is fundamentally incapable of replacing distributed tissues and structures with a high degree of interconnectivity to other tissues in the body. The aim of ICT is to form a bridge between these two main pillars of regenerative medicine, extending the efficacy of cell therapies beyond a patch for existing cell loss and accomplishing the aim of tissue and organ engineering (i.e. the replacement and regeneration of whole tissues and organs) while potentially remaining free of some of their present limitations,” said Giovanni Santostasi, co-author on the paper and a researcher at the Feinberg School of Medicine, Northwestern University.

While future iterations of the therapy could use patient-derived cells, such as ESCs derived via somatic cell nuclear transfer (SCNT) or iPSCs derived from nuclear reprogramming, shorter-term applications would likely use existing stem cell lines immunologically matched to the patient via HLA matching. The authors contend that the cloning of adult organisms with normal lifespans from adult somatic cells testifies to the fact that adult cells can be rejuvenated and used to produce a sufficient quantity of daughter cells to replace the sum of cells constituting adult organisms, and that serial cloning experiments (in which this process is done iteratively, using an adult cell of each subsequent generation to derive the next) attests to this fact even more strongly.

“ICT could theoretically enable the controlled turnover and rejuvenation of aged tissues. The technique is particularly applicable to tissues that are not amenable to growth ex vivo and implantation (as with solid organs) – such as the vascular, lymphatic, and nervous systems. The method relies upon targeted ablation of old, damaged and/or senescent cells, coupled with a titrated replacement with patient-derived semi-differentiated stem and progenitor cells. By gradually replacing the old cells with new cells, entire tissues can be replaced in situ. The body naturally turns over tissues, but not all tissues and perhaps not optimally. I am reminded of the quote attributed to Heraclitus: ‘No man ever steps in the same river twice, for it’s not the same river and he’s not the same man,'” said Sebastian Aguiar, a coauthor on the paper and researcher at the Swammerdam Institute of Life Sciences, University of Amsterdam.

“Reversing aging in humans will require a multi-step approach at multiple levels of the organismal organization. In situ targeted ablation of the senescent cells and regeneration will be an important component of comprehensive anti-aging therapies,” said Alex Zhavoronkov, Chief Science Officer of the Biogerontology Research Foundation.

The researchers originally proposed ICT in 2016 in the context of biomedical gerontology as a possible means of preventing and/or negating age-related phenotypic deviation for the purposes of healthspan extension, and in this new paper they refine the methodological underpinnings of the approach, take a closer look at potential complications and strategies for their deterrence, and analyze ICT in the context of regenerative medicine as an intervention for a broader range of conditions based on disease or dysfunction at the cellular and intercellular level, with potential utilities absent from traditional cell therapies and tissue/organ engineering, the two main pillars of regenerative medicine. The intervention is still very much conceptual, and any potential utilities over other therapeutic modalities within regenerative medicine would need to be verified via preclinical studies, but their hope is to stimulate further research at this interface between geroscience and regenerative medicine.

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The paper is available here.

About the Biogerontology Research Foundation:

The Biogerontology Research Foundation is a UK non-profit research foundation and public policy center seeking to fill a gap within the research community, whereby the current scientific understanding of the ageing process is not yet being sufficiently exploited to produce effective medical interventions. The BGRF funds and conducts research which, building on the body of knowledge about how ageing happens, aims to develop biotechnological interventions to remediate the molecular and cellular deficits which accumulate with age and which underlie the ill-health of old age. Addressing ageing damage at this most fundamental level will provide an important opportunity to produce the effective, lasting treatments for the diseases and disabilities of ageing, required to improve quality of life in the elderly. The BGRF seeks to use the entire scope of modern biotechnology to attack the changes that take place in the course of ageing, and to address not just the symptoms of age-related diseases but also the mechanisms of those diseases.