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In Support of “Unfit for the Future”: When the Vessel is Unfit for the Task – Article by Sarah Lim

In Support of “Unfit for the Future”: When the Vessel is Unfit for the Task – Article by Sarah Lim

Sarah Lim


This essay has been submitted for publication to the Journal of Posthuman Studies.

This essay is written in support of the ideas presented by Julian Savulescu and Ingmar Persson in their book Unfit for the Future: the Need for Moral Enhancement. I will argue that Savulescu and Persson’s arguments for moral bioenhancement should be given more serious consideration, on the grounds that moral bioenhancement will most likely be humanity’s best chance at ensuring its future ethical progress, since our current achievements in rapid ethical progress have been highly contingent on economic progress and an increasing quality of life. As a vehicle for for ethical progress, this is becoming increasingly untenable as the world enters a new period of resource scarcity brought about by the ravages of climate change. This essay will also respond to some of the claims against human genetic enhancement, and transhumanism in general, made by critic John Gray. Finally, the concluding remarks of this essay will examine a possible long-term drawback to moral bioenhancement which has not net been raised by Savulescu’s critics thus far – namely, that genetically altering future human beings to be less aggressive could unintentionally result in them becoming complacent to a point of lacking self-preservation.

Maslow and Malthus

Ethical philosophers in Steven Pinker’s camp may argue that the consideration of moral bioenhancement is absurd because moral education has apparently been sufficient enough to bring forth radical moral progress in terms of civil liberties in the 20th and 21st centuries. The 20th century heralded in never-before-seen progress in terms of the civil rights granted to women, ethnic minorities, LGBT+ people, and the working class. As Pinker points out, crime rates plummeted over the past 150 years, and so has the total number of wars being fought throughout the world. Savulescu admits that this is a valid point.

However, Savulescu’s main point of contention is that while the overall rates of violent crime have been drastically reduced, rapid advancements in technology have enabled rouge individuals to inflict more mass damage than at any other point in human history. While overall rates of interpersonal violence and warfare are decreasing, advancements in technology have exponentially increased the ability of individual actors to inflict harm on others to a greater extent than at any other point in human history. It takes just one lone Unabomber-type anarchist to genetically engineer a strain of smallpox virus in a backyard laboratory, to start a pandemic killing millions of innocent people, argues Savulescu. A statistic he constantly cites is that 1% of the overall human population are psychopaths. This means that there are approximately 77 million psychopaths alive today.

I would like to raise a further point in support of Savulescu’s argument. I would argue that the exceptional progress in ethics and civil rights that the developed world has witnessed in the last century has been the result of unprecedented levels of economic growth and vast improvements in the average quality of life. The life spans, health spans, and accessibility of food, medicine, and consumer goods seen in developed economies today would have been an unbelievable utopian dream as little as 250 years ago. One of X Prize Foundation chairman Peter Diamandis’s favorite quips is that our standard of living has increased so exponentially that the average lower-income American has a far higher quality of life than the wealthiest of robber barons did in the 19th century.

As Pinker himself points out, the first moral philosophies of the Axial Age arose when our ancestors finally became agriculturally productive enough to no longer worry about basic survival. Once they had roofs over their heads and sufficient grain stores, they could begin to wax lyrical about philosophy, the meaning of life, and the place of the individual in wider society. Arguably, the same correlation was strongly demonstrated in the post-World War II era in the developed economies of the world. Once the population’s basic needs are not just met, but they are also provided with access to higher education and a burgeoning variety of consumer goods, they’re much less likely to be in conflict with “out” groups over scarce resources. Similarly, incredible advancements in maternal healthcare and birth control played a major role in the socio-economic emancipation of women.

Our ethical progress being highly contingent on economic progress and quality of life should concern us for one major reason – climate change and the resource scarcity that follows it. The UN estimates that the world’s population will hit 9.8 billion by 2050. At the same time, food insecurity and water scarcity are going to become increasingly common. According to UNICEF, 1.3 million people in Madagascar are now at risk of malnutrition, due to food shortages caused by cyclones and droughts. There could as many as 25 million more children worldwide suffering from climate-change-caused malnutrition by the middle of this century. This is on top of the 149 million malnourished children below 5 years old, who are already suffering from stunted growth, as of 2019.

This is the worst-case scenario that climate-change doomsdayers and authors of fiction revolving around dystopian civilizational collapse keep on warning us of. There is a legitimate fear that a rapid dwindling of access to food, medical care, and clean water could lead currently progressive developed economies to descend back into pre-Enlightenment levels of barbarism. Looting and black markets for necessities could flourish, while riots break out over access to food and medical supplies. Ostensibly, worsening scarcity could encourage the proliferation of human trafficking, especially of females from desperate families. The idea is often dismissed as wildly speculative alarmist screed by a considerable number of middle-income city dwellers living in developed nations. Food shortages caused by climate change have mostly affected the sub-Saharan Africa and India, where they’re far out of sight and out of mind to most people in developed economies.

However, the World Bank estimates that 140 million people could become refugees by 2050, as a result of climate change. These populations will predominantly be from Africa, the Middle East, and South Asia, but it is likely that a significant percentage of them will seek asylum in Europe and America. And developed Western economies will only be spared from the worst effects of climate change for so long. North Carolina has already been afflicted by severe flooding caused by Hurricane Florence in 2018, just as it was  affected by Hurricane Matthew which had struck two years earlier. Climate journalist David Wallace-Wells has gone so far as to claim that a four degree increase in global temperature by 2100 could result in resource scarcity so severe, that it will effectively double the number of wars we see in the world today.

Savulescu argues that the fact that we’ve already let climate change and global income inequality get this bad is itself proof that we’re naturally hardwired towards selfishness and short-term goals.

A Response to John Gray

As one of the most well-known critics of transhumanism, John Gray has said that it is naive to dream that humanity’s future will somehow be dramatically safer, more humane, and more rational than its past. Gray claims that humanity’s pursuit of moral progress will ultimately never see true fruition, because our proclivities towards irrationality and self-preservation will inevitably override our utopian goals in the long run. Gray cites the example of torture, which was formally banned in various treaties across Europe during the 20th century. However, this hasn’t stopped the US from torturing prisoners of war with all sorts of brutal methods, in Afghanistan and Iraq. Gray claims that this is proof that moral progress can be rolled back just as easily as it is made. Justin E. H. Smith makes similar arguments about the inherent, biologically-influenced cognitive limits of human rational thinking, although he does not explicitly criticise transhumanism itself. And Savulescu agrees with him. Throughout their argument, both Savulescu and Persson hammer home the assertion that humans have a much greater predilection towards violence than altruism.

But here Gray is making a major assumption – that future generations of human beings will continue to have the same genetically-predisposed psychology and cognitive capabilities as we currently do. Over millennia, we have been trying to adapt humanity to a task that evolution did not predispose us towards. We’ve effectively been trying to carry water from a well using a colander. We might try to stop the water from leaking out from the colander as best we can by cupping its sides and bottom with our bare palms, but Savulescu is proposing a radically different solution; that we should re-model the colander into a proper soup bowl.

It seems that Gray is overlooking some of his own circular reasoning which he uses to perpetuate his arguments against transhumanist principles and genetic enhancement. He argues that humanity will never truly be able to overcome our worst proclivities towards violence and selfishness. However, he simultaneously argues that endeavoring to enhance our cognitive capabilities and dispositions towards rationality and altruism are a lost cause that will be ultimately futile. Following Gray’s line of reasoning will effectively keep humanity stuck in a catch-22 situation where we’re damned if we do and damned if we don’t. Gray is telling us that we need to resign ourselves to never being able to have a proper water-holding vessel while simultaneously discouraging us from considering the possibility of going to a workshop to weld the holes in our colander shut.

Windows of Opportunity

There is one final reason for which I will argue for greater urgency in considering Savulescu’s proposal seriously. Namely, we are currently have a very rare window of opportunity to execute it practically. If Gray is right about the likelihood that moral progress can be rolled back more easily than it is made, then he should acknowledge that we need to take full advantage of the current moral progress in developed economies, while we still have the chance to. Rapid advancements in CRISPR technologies and gene-editing are increasing the practical viability of moral bioenhancement without the consumption of neurotransmitters. Savulescu argues that we need to strike while the iron is hot; while the world economy is still relatively healthy and while STEM fields are still receiving billions in funding for research and development.

If nothing else, a rather intellectually sparse appeal to novelty can be made in defence of Savulescu’s proposal. Given that climate change could be the greatest existential risk humanity has ever faced in its whole history to date, we should begin considering more radical options to deal with its worst ravages. The limited faculties of rationality and altruism which nature has saddled us with have brought us millennia of warfare, genocide, radical inequality in resource distribution, and sexual violence. We keep on saying “never again” after every single cataclysmic man-made tragedy, but “again” still keeps on happening. Now is as good a time as ever to consider the possibility that humanity’s cognitive faculties are themselves fundamentally flawed, and inadequate to cope with the seemingly insurmountable challenges that lie ahead of us.

A Possible Future Negative Consequence of Moral Bioenhancement to be Considered

Multiple objections to Savulescu’s proposal have been raised by authors such as Alexander Thomas and Rebecca Bennett. I would like to raise another possible objection to moral bioenhancement, although I myself am a proponent of it. A possible unforeseen consequence of radically genetically reprogramming homo sapiens to be significantly less selfish and prone to aggression could be that this will simultaneously destroy our drive for self-improvement. One could argue that the only reason human beings have made it far enough to become the most technologically advanced and powerful species in our solar system was precisely because our drive for self-preservation and insatiable desire for an ever-increasing quality of life. You could claim that if we had just remained content to be hunter-gatherers, we would never have gotten to the level of civilization we’re at now. It’s more likely that we would have gone extinct on the savannah like our other hominid cousins, who were not homo sapiens.

Our inability to be satisfied with the naturally-determined status quo is the very reason the transhumanist movement itself exists. What happens, then, if we genetically re-dispose homo sapiens to become more selfless and less aggressive? Could this policy ironically backfire and create future generations of human beings who become complacent about technological progress and self-improvement? Furthermore, what happens if these future generations of morally bioenhanced human beings face new existential threats which require them to act urgently? What happens if they face an asteroid collision or a potential extraterrestrial invasion (although the latter seems to be far less likely)? We don’t want to end up genetically engineering future generations of human beings who are so devoid of self-preservation that they accept extinction as an outcome they should just peacefully resign themselves to. And if human beings become a space-faring species and end up making contact with a highly-advanced imperialist alien species bent on galaxy-wide colonization, our future generations will have to take up arms in self-defence.

This raises the question of whether it might be possible to simultaneously increase the human propensity towards altruism and non-violence towards other human beings, while still preserving the human predisposition towards ensuring our overall survival and well-being. If such a radical re-programming of humanity’s cognitive disposition is possible, it’s going to be a very delicate balancing act. This major shortcoming is one that proponents of moral bioenhancement have not yet formulated a plausible safety net for. Techno-utopian advocates claim that we could one day create a powerful artificial intelligence programme that will indefinitely protect humanity against unforeseen attacks from extraterrestrials or possible natural catastrophes. More serious discussion needs to be devoted to finding possible ways to make moral bioenhancement as realistically viable as possible.

Conclusion

The arguments put forth by Savulescu in Unfit for the Future should be reviewed with greater urgency and thoughtful consideration, and this essay has argued in favour of this appeal. We cannot take the great strides in civil rights made in the last 100 years, which have been heavily dependent on economic development and the growth of the capitalist world economy, for granted. As resource scarcity brought about by climate change looms on the near horizon, the very system which the 20th and 21st centuries’ great ethical progress has been contingent upon threatens to crumble. Gray is right in arguing that the human animal is fundamentally flawed and that repeated historical attempts at better models of moral systems have failed to truly reform humanity. And this is where Savulescu proposes a controversial answer to Gray’s resignation to humanity’s impending self-destruction. We must consider reforming the human animal itself. As the field of gene-editing and the development of impulse-controlling neurotransmitter drugs continue to show great promise, world governments and private institutions should begin to view these as viable options to creating a less short-sighted, less-aggressive, and more rational version of homo sapiens 2.0. There are only so many more global-scale man-made catastrophes that mankind can further inflict upon itself and the planet, before this radical proposal is finally undertaken as a last resort.

Sarah Lim is a fourth-year political science major at the National University of Singapore. She is a proud supporter of the transhumanist movement and aims to do her best to promote transhumanism and progress towards the Singularity.

The Hedonistic Imperative – The End of Suffering – Video by David Pearce and Duarte Baltazar

The Hedonistic Imperative – The End of Suffering – Video by David Pearce and Duarte Baltazar

logo_bgDavid Pearce
Duarte Baltazar


Editor’s Note: The U.S. Transhumanist Party has featured this brief video highlighting the thinking of one of our members, transhumanist philosopher David Pearce, on the abolition of suffering. This video, produced by Duarte Baltazar of Utopian Focus, illustrates one possibility for transhumanist messages reaching larger audiences through concise, powerful films that distill particular transhumanist concepts and aspirations.  

~ Gennady Stolyarov II, Chairman, United States Transhumanist Party, April 15, 2018

Description by Duarte Baltazar of Utopian Focus: Learn more about Utopian Focus at https://utopianfocus.com.

Excerpt from “The Hedonistic Imperative” by David Pearce. Read the full essay at https://www.hedweb.com.

States of sublime well-being are destined to become the genetically pre-programmed norm of mental health. It is predicted that the world’s last unpleasant experience will be a precisely dateable event.

The Hedonistic Imperative outlines how genetic engineering and nanotechnology will abolish suffering in all sentient life.

The abolitionist project is hugely ambitious but technically feasible. It is also instrumentally rational and morally urgent. The metabolic pathways of pain and malaise evolved because they served the fitness of our genes in the ancestral environment. They will be replaced by a different sort of neural architecture – a motivational system based on heritable gradients of bliss.

States of sublime well-being are destined to become the genetically pre-programmed norm of mental health. It is predicted that the world’s last unpleasant experience will be a precisely dateable event.

Two hundred years ago, powerful synthetic pain-killers and surgical anesthetics were unknown. The notion that physical pain could be banished from most people’s lives would have seemed absurd. Today most of us in the technically advanced nations take its routine absence for granted. The prospect that what we describe as psychological pain, too, could ever be banished is equally counter-intuitive. The feasibility of its abolition turns its deliberate retention into an issue of social policy and ethical choice.

Video Editing, Post-Production and Soundtrack by Duarte Baltazar

Utopian Focus: https://facebook.com/utopianfocus

Narration by Elvis Andrumora

Circle of Synths: https://www.circleofsynths.com

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.

7. Payne, R., Muenchhoff, M., Mann, J., Roberts, H. E., Matthews, P., Adland, E., … Goulder, P. J. R. (2014). Impact of HLA-driven HIV adaptation on virulence in populations of high HIV seroprevalence. Proceedings of the National Academy of Sciences of the United States of America111(50), E5393–E5400. http://doi.org/10.1073/pnas.1413339111

8. Eloe-Fadrosh, E. A., & Rasko, D. A. (2013). The Human Microbiome: From Symbiosis to Pathogenesis. Annual Review of Medicine64, 145–163. http://doi.org/10.1146/annurev-med-010312-133513

9. Houldcroft, C. J., & Kellam, P. (2015). Host genetics of Epstein–Barr virus infection, latency and disease. Reviews in Medical Virology25(2), 71–84. http://doi.org/10.1002/rmv.1816

10. Haifeng Chen. (2015) Adeno-associated virus vectors for human gene therapy. Published by Baishideng Publishing Group Inc. doi: 10.5496/wjmg.v5.i3.28

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Being Excited About Failure – Article by Martin van der Kroon

Being Excited About Failure – Article by Martin van der Kroon

Martin van der Kroon


The much hyped CRISPR-Cas9 genome-editing technique often explained as being the ‘DNA scissors’ or the ‘cut and paste’ technique, has had a setback, and this has me excited.

CRISPR-Cas9 has has the scientific community, and in particular those involved in research and development of genome editing, raving over the roughly past 3 years. It is hailed as a cheap and fast way to edit genomes with great accuracy compared to other genome-editing techniques, and this is true. Now however, researchers have found CRISPR-Cas9 to have some annoying side-effects. The side-effects were found in mice who had their blindness corrected but also caused mutations in other parts of the DNA sequence, roughly 1500 mutations. It is unknown what the consequences of the mutations are at this moment.

“Why am I excited about this setback?” you might ask.

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