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Our Cells Will Be Guided and Protected by Machines – Article by Reason

Our Cells Will Be Guided and Protected by Machines – Article by Reason

The New Renaissance Hat
Reason
September 21, 2014
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A gulf presently lies between the nanoscale engineering of materials science on the one hand and the manipulation and understanding of evolved biological machinery on the other. In time that gulf will close: future industries will be capable of producing and controlling entirely artificial machines that integrate with, enhance, or replace our natural biological machines. Meanwhile biologists will be manufacturing ever more artificial and enhanced versions of cellular components, finding ways to make them better: evolution has rarely produced the best design possible for any given circumstance. Both sides will work towards one another and eventually meet in the middle.

Insofar as aging goes, a process of accumulating damage and malfunction in our biology, it is likely that this will first be successfully addressed and brought under medical control by producing various clearly envisaged ways to repair and maintain our cells just as they are: remove the damage, restore youthful function, and repeat as necessary. We stand much closer to that goal than the far more ambitious undertaking of building a better, more resilient, more easily repaired cell – a biology 2.0 if you like. That will happen, however. Our near descendants will be as much artificial as natural, and more capable and healthier for it.

The introduction of machinery to form a new human biology won’t happen all at once, however, and it isn’t entirely a far future prospect. There will be early gains and prototypes, the insertion of simpler types of machine into our cells for specific narrow purposes: sequestering specific proteins or wastes, or as drug factories to produce a compound in response to circumstances, or any one of a number of other similar tasks. If you want to consider nanoparticles or engineered assemblies of proteins capable of simple decision tree operations as machines then this has already happened in the lab:

Researchers Make Important Step Towards Creating Medical Nanorobots

Quote:

Researchers [have] have made an important step towards creating medical nanorobots. They discovered a way of enabling nano- and microparticles to produce logical calculations using a variety of biochemical reactions. Many scientists believe logical operations inside cells or in artificial biomolecular systems to be a way of controlling biological processes and creating full-fledged micro-and nano-robots, which can, for example, deliver drugs on schedule to those tissues where they are needed.

Further, there is a whole branch of cell research that involves finding ways to safely introduce ever larger objects into living cells, such as micrometer-scale constructs. In an age in which the state of the art for engineering computational devices is the creation of 14 nanometer features, there is a lot that might be accomplished in the years ahead with the space contained within a 1000 nanometer diameter sphere.

Introducing Micrometer-Sized Artificial Objects into Live Cells: A Method for Cell-Giant Unilamellar Vesicle Electrofusion

Quote:

Direct introduction of functional objects into living cells is a major topic in biology, medicine, and engineering studies, since such techniques facilitate manipulation of cells and allows one to change their functional properties arbitrarily. In order to introduce various objects into cells, several methods have been developed, for example, endocytosis and macropinocytosis. Nonetheless, the sizes of introducible objects are largely limited: up to several hundred nanometers and a few micrometers in diameter. In addition, the uptake of objects is dependent on cell type, and neither endocytosis nor macropinocytosis occur, for example, in lymphocytes. Even after successful endocytosis, incorporated objects are transported to the endosomes; they are then eventually transferred to the lysosome, in which acidic hydrolases degrade the materials. Hence, these two systems are not particularly suitable for introduction of functionally active molecules and objects.To overcome these obstacles, novel delivery systems have been contrived, such as cationic liposomes and nanomicelles, that are used for gene transfer; yet, only nucleic acids that are limited to a few hundred nanometers in size can be introduced. By employing peptide vectors, comparatively larger materials can be introduced into cells, although the size limit of peptides and beads is approximately 50nm, which is again insufficient for delivery of objects, such as DNA origami and larger functional beads.

Here, we report a method for introducing large objects of up to a micrometer in diameter into cultured mammalian cells by electrofusion of giant unilamellar vesicles (GUVs). We prepared GUVs containing various artificial objects using a water-in-oil emulsion centrifugation method. GUVs and dispersed HeLa cells were exposed to an alternating current (AC) field to induce a linear cell-GUV alignment, and then a direct current (DC) pulse was applied to facilitate transient electrofusion.

With uniformly sized fluorescent beads as size indexes, we successfully and efficiently introduced beads of 1 µm in diameter into living cells along with a plasmid mammalian expression vector. Our electrofusion did not affect cell viability. After the electrofusion, cells proliferated normally until confluence was reached, and the introduced fluorescent beads were inherited during cell division. Analysis by both confocal microscopy and flow cytometry supported these findings. As an alternative approach, we also introduced a designed nanostructure (DNA origami) into live cells. The results we report here represent a milestone for designing artificial symbiosis of functionally active objects (such as micro-machines) in living cells. Moreover, our technique can be used for drug delivery, tissue engineering, and cell manipulation.

Cell machinery will be a burgeoning medical industry of the 2030s, I imagine. To my eyes the greatest challenge in all of this is less the mass production of useful machines per se, and more the coordination and control of a body full of tens of trillions of such machines, perhaps from varied manufacturers, introduced for different goals, and over timescales long in comparison to business cycles and technological progress. That isn’t insurmountable, but it sounds like a much harder problem than those inherent in designing these machines and demonstrating them to be useful in cell cultures. It is a challenge on a scale of complexity that exceeds that of managing our present global communications network by many orders of magnitude. If you’ve been wondering what exactly it is we’ll be doing with the vast computational power available to us in the decades ahead, given that this metric continues to double every 18 months or so, here is one candidate.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 
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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.

Progress for The Longevity Meme Folding@home Team – Update of August 4, 2014 – by G. Stolyarov II

Progress for The Longevity Meme Folding@home Team – Update of August 4, 2014 – by G. Stolyarov II

The New Renaissance Hat
G. Stolyarov II
August 4, 2014
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I am pleased to announce significant progress for The Longevity Meme Folding@home team – a group of volunteers who donate their computing power to perform protein-folding simulations that could one day result in cures for major diseases and the lengthening of human lifespans.

Statistics for the full month of July 2014 show significant improvement compared to both May and June – a total of 3,957,851 points earned by team members, up from 2,368,216 in June (a 67.1% increase) and from 1,624,448 in May (a 143.6% increase). The number of workunits processed has risen even more astronomically, from 1,396 in May to 1,963 in June, to 7,814 in July – a near-quadrupling in one month. Here is a summary of monthly production for The Longevity Meme team from the Extreme Overclocking statistics page. Longevity_Meme_Folding_Statistics_8-4-2014The increase is attributable to a rise in active member participation. Many previously active members have resumed folding, and new contributors have joined us. My offering of five tiers of Open Badges for contributors who reach certain point thresholds has attracted at least one user thus far – RonnyR (Ronny Risøen), whom I would like to thank for his tremendous contribution thus far – nearly 2.5 million points in just three months! He is The Longevity Meme team’s most rapid producer at present. Other substantial contributions during the recent months were made by users ralmcruz, TMichael, Gennady Stolyarov II (myself), LongandLasting, Volcanic, dreilopz, and sigma957. All of these users have earned Open Badges for their work and should contact me at gennadystolyarovii@gmail.com so that I could send them a code for claiming their badges.

Participation in protein-folding initiatives such as Folding@home is an excellent way to promote the message of indefinite life extension and to personally accelerate the advent of research breakthroughs that could actually lengthen our lives. We have made impressive strides forward, but we still need additional contributors to raise The Longevity Meme team’s ranking on the Folding@home leaderboard and thereby raise the prominence and reach of life-extension ideas. Join us today!

“Protein Folding for Life Extension” Open Badges for Folding@home Participation – Post by G. Stolyarov II

“Protein Folding for Life Extension” Open Badges for Folding@home Participation – Post by G. Stolyarov II

The New Renaissance Hat
G. Stolyarov II
June 8, 2014
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I am pleased to offer five levels of Open Badges as rewards for contributing computing power to the Folding@home project at http://folding.stanford.edu/, which enables anyone in the world to devote computational resources to protein-folding simulations that help advance the fight against a multitude of diseases – such as Alzheimer’s Disease, Parkinson’s Disease, and many cancers. The Longevity Meme Folding@home team seeks to promote increased participation in Folding@home as one way to combat disease and help dramatically lengthen human lifespans within our lifetimes, with the goal of enabling humans to live lives without any upper limit.

These badges were designed by the artist and illustrator Wendy Stolyarov and is issued by  The Rational Argumentator, in conjunction with LongeCity and the Longevity Meme Folding@home team.

You can store these digital badges and share them via Mozilla Backpack to display your achievements to others. The following are the qualifying criteria for each badge:

Level 1: 5,000 points earned on Folding@home;

Level 2: 10,000 points earned on Folding@home;

Level 3: 50,000 points earned on Folding@home;

Level 4: 100,000 points earned on Folding@home;

Level 5: 500,000 points earned on Folding@home.

To request a badge, simply send an e-mail to gennadystolyarovii@gmail.com. Include your user name on Folding@home so that your points earned could be verified. You can earn a badge no matter what team you are on, if any, as everyone’s commitment of resources to the protein-folding effort helps the prospects of indefinite life extension. However, you are also encouraged to join The Longevity Meme team in order to help improve its ranking and raise public awareness of the effort life-extension activists are putting into the fight against disease.

Level 1 Folder - Protein Folding for Life Extension

Level 2 Folder - Protein Folding for Life Extension

Level 1 Folder - Protein Folding for Life Extension

Level 4 Folder - Protein Folding for Life Extension

Level 5 Folder - Protein Folding for Life Extension

Life-Extension Activism Opportunities for All – Article by G. Stolyarov II

Life-Extension Activism Opportunities for All – Article by G. Stolyarov II

The New Renaissance Hat
G. Stolyarov II
June 5, 2014
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You do not need to be a biologist or medical doctor to help hasten the arrival of indefinite life extension. An important array of activist endeavors, which are laying the groundwork for the eventual achievement of unlimited lifespans, can be implemented by anybody. They range from giving out books to playing games to simply running one’s computer – all the while making important contributions to scientific progress and the receptiveness of the general culture to the feasibility and desirability of indefinite longevity.

If you want to glimpse the possibilities in 90 seconds, watch my recent video, “What Anyone Can Do to Advance Indefinite Life Extension”.

In this article, I offer a more detailed overview of some immediately available activism options that anyone can pursue. The time commitment involved in each ranges from minimal to modest, but virtually any of them can fit into the schedule of anyone who recognizes the value of this amazing life we have and the importance of prolonging it as far as possible.

Movement for Indefinite Life Extension (MILE)

MILE_Logo
The Movement for Indefinite Life Extension (MILE) is not a formal organization, but rather a coalition of activists working toward the common goal of achieving indefinite lifespans for people alive today. The MILE coordinates projects and shares articles, images, and news stories via its Facebook group – also accessible using the URL http://themile.info. One of the MILE’s major purposes is to raise awareness of the feasibility and desirability of indefinite life extension and to create a critical mass of support for this most vital of goals. The number of “likes” on the MILE Facebook page is a concise indicator of the movement’s reach, and the eventual goal of the MILE is to achieve 8 million likes by July 17, 2017. Following an incremental approach, the MILE seeks to raise its support by an order of magnitude each year. The goal of 800 supporters was readily exceeded prior to July 17, 2013, and the MILE has launched a concerted effort to reach its Year 2 goal of 8,000 supporters by July 17, 2014. Eric Schulke, who spearheads and coordinates the efforts of the MILE, has launched the MILE Year 2 Goal Fundraiser to fund hundreds of dollars of Facebook advertisements that have already shown success in spreading the message of indefinite life extension to new demographics.

I am proud to have contributed resources to run several ads for MILE that incorporate the core message and the cover image of my children’s book Death is Wrong. These MILE/Death is Wrong ads were designed by my wife and illustrator Wendy Stolyarov and are accompanied by the following text:

Death is WRONG.
Together we can fight it.
Join the Movement for Indefinite Life Extension.

Reaper_MILE_Ad_FBDIW_MILE_AdTo help the MILE reach its Year 2 goal, you can start by clicking the “Like” button on the MILE Facebook page. Beyond that, if you would like to contribute to the advertising campaign and even develop your own custom advertisement that conveys the message of indefinite life extension, this would go a long way toward building the critical mass needed to catalyze public support for life-extension research.

Death is Wrong Book Distribution to Children

DIW_HannaAfter the successful conclusion on April 23, 2014, of my Indiegogo fundraiser to spread over 1,000 copies of the illustrated children’s book Death is Wrong to kids, free of cost to them, I have worked assiduously to coordinate a worldwide distribution effort. Already, 644 out of the 1,029 total available books have been sent to longevity activists throughout the world. Countries where the books have been shipped thus far include the United States, Canada, Mexico, the United Kingdom, the Netherlands, Poland, India, Indonesia, and Singapore. Tens of dedicated longevity supporters have already come forward to request absolutely free shipments of books, but we need more activists to help us distribute the remaining 385 books in their local areas.

Recipients have wide discretion to use their creativity in how to offer the Death is Wrong books to children, as long as the books are made available free of cost and are not resold. Books may be given away to kids directly, lent to multiple kids, given to schools and libraries that will accept them, or used at public readings – among possible other options.

The early successes of the book-distribution effort are among the most heartening and encouraging developments I have observed. Here are some photographs that longevity activists have sent in of their book shipments.

DIW_Amechazurra_ShipmentDIW_Books_Received_CvdB_3
DIW_Books_Received

Here is a charming interview by Aleksander Kelley of his sister Hanna, who is spreading Death is Wrong to the kids she knows.

Help make future scenes like this happen. Requesting a shipment of Death is Wrong books is simple. Send me an e-mail to gennadystolyarovii@gmail.com with (i) your name, (ii) your mailing address, (iii) your statement of support for indefinite life extension, (iv) the number of copies of Death is Wrong requested, and (v) your plan for spreading the books to children, free of cost to them.

Once the shipments arrive, any additional images and videos of the books and events at which they are shared would be most welcome. They can help spread the message of indefinite life extension even further and show the world that the momentum for this cause continues to grow.

Distributed Computing for Medical Science

Would you like to help cure cancer, Alzheimer’s disease, Huntington’s disease, and other deadly ailments, just by running your computer? Most people’s computers spend much time absolutely idle; how about putting that idle time to good use, at minimal additional cost? Distributed computing initiatives such as Folding@home, Rosetta@home, and World Community Grid are absolutely free to join. You just need to download a program that runs the calculations involved in protein-folding simulations and other research efforts while you are not using your computer. Already, these distributed computing initiatives have led to several major medical research breakthroughs, such as this one by Chiba Cancer Center in Japan, which has identified seven drug candidates in the fight against childhood cancer. You can read more about the applications of protein-folding simulations to disease research in this brief post by David Baker of the University of Washington.

While no single medical breakthrough will achieve indefinite lifespans yet, every victory against death and diseases will help us approach that goal. The more of us survive the common killers of our time, the more of us stand a chance of personally witnessing the arrival of longevity escape velocity.

As an additional way to raise the profile of the ideas of indefinite life extension, it is recommended to join a distributed-computing team that explicitly embraces the struggle against senescence and death. On Folding@home, The Longevity Meme team has been folding for years and is ranked 156th out of 220,186 teams as of June 5, 2014. I am spearheading a collaborative effort between The Longevity Meme team, LongeCity, and my online magzine – The Rational Argumentator – to attract renewed participation in Folding@home and The Longevity Meme team among longevity advocates. To provide an additional incentive to join, I am offering a series of five Protein Folding for Life Extension Open Badges, designed by Wendy Stolyarov and available via Badg.us.

FaH-Square-L1 FaH-Square-L2 FaH-Square-L3 FaH-Square-L4 FaH-Square-L5These are badges that you can store and share via Mozilla Backpack to share your achievements with others. The following are the qualifying criteria for each badge:

Level 1: 5,000 points earned on Folding@home;

Level 2: 10,000 points earned on Folding@home;

Level 3: 50,000 points earned on Folding@home;

Level 4: 100,000 points earned on Folding@home;

Level 5: 500,000 points earned on Folding@home.

To request a badge, simply send an e-mail to gennadystolyarovii@gmail.com. Include your user name on Folding@home so that your points earned could be verified. You can earn a badge no matter what team you are on, if any, as everyone’s commitment of resources to the protein-folding effort helps the prospects of indefinite life extension. However, you are also encouraged to join The Longevity Meme team in order to help improve its ranking and raise public awareness of the effort life-extension activists are putting into the fight against disease.

On Rosetta@home, the LongeCity team explicitly embraces the ideas of indefinite life extension. On World Community Grid, the Endthedisease team supports life extension and has been involved in numerous disease-fighting computational efforts since 2007. Later this year, the Endthedisease team is anticipated to begin running contests with prizes for top contributors.

Games to Fight Disease

By flying a spaceship through an asteroid field in a computer game, you can help cancer researchers analyze data at a much faster rate than they could before. Play to Cure: Genes in Space is a mobile game released by Cancer Research UK, which anyone with a tablet or mobile phone can play for free. The stated aim of this game is to hasten the day when all cancers are cured – which is, incidentally, the key objective of one of the seven prongs of Dr. Aubrey de Grey’s SENS approach; Dr. de Grey has emphasized that cancer is by far the predominant way by which age-related nuclear mutations harm us.

You can read about the mechanics of and science behind Play to Cure here and watch this video introduction to the game.

Foldit is another free game that enthusiasts of life-extension research can play in order to add the human touch to protein-folding simulations. In 2011, Foldit players discovered the protein structure of a retroviral protease of the Mason-Pfizer monkey virus, an AIDS-like disease in monkeys.

See this list from the Citizen Science Center for more possibilities regarding games you could play and simultaneously participate in innovative citizen-science initiatives – including many devoted to the fight against disease. Games hold out the promise of enabling monumental contributions to scientific research by the general public. A game designed to be sufficiently engaging could attract thousands of non-scientists to do the work that research scientists could conceivably outsource in order to accelerate the rate at which certain kinds of data analysis are performed. The more quickly scientists can iterate through their experiments as a result, the sooner the cures to major diseases will arrive.

Conclusion

Of course, I would urge all life-extension supporters to donate even modest amounts of money to research and advocacy organizations such as the SENS Research Foundation and the Methuselah Foundation, as well as crowdfunded life-extension research projects that are being undertaken with increasing frequency. Yet, I hope that this overview has led readers to recognize that much can be done in addition to monetary donations. Integrate the active pursuit of indefinite longevity into your life, and you will continue to find easy but extremely important ways to become part of the solution to the most pressing problem of all time. Through our efforts, we will hopefully someday be able to celebrate humankind’s greatest victories in the fight against our mutual enemy: death.

What Anyone Can Do to Advance Indefinite Life Extension – Video by G. Stolyarov II

What Anyone Can Do to Advance Indefinite Life Extension – Video by G. Stolyarov II

Mr. Stolyarov provides a quick overview of ideas that anyone can implement to accelerate the pace of technological progress and bring about indefinite life extension for many who are alive today.

This is Mr. Stolyarov’s entry in the MILE Video Contest.

References
SENS Research Foundation
Methuselah Foundation
MILE – Movement for Indefinite Life Extension
Folding@home
The Longevity Meme Folding@home Team
Open Badges for Participating in Folding@home
Rosetta@home
World Community Grid
Foldit
Play to Cure

Immortality: Material or Ethereal? Nanotech Does Both! – Article by Franco Cortese

Immortality: Material or Ethereal? Nanotech Does Both! – Article by Franco Cortese

The New Renaissance Hat
Franco Cortese
May 11, 2013
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This essay is the second chapter in Franco Cortese’s forthcoming e-book, I Shall Not Go Quietly Into That Good Night!: My Quest to Cure Death, published by the Center for Transhumanity. The first chapter was previously published on The Rational Argumentator as “The Moral Imperative and Technical Feasibility of Defeating Death“.

In August 2006 I conceived of the initial cybernetic brain-transplant procedure. It originated from a very simple, even intuitive sentiment: if there were heart and lung machines and prosthetic organs, then why couldn’t these be integrated in combination with modern (and future) robotics to keep the brain alive past the death of its biological body? I saw a possibility, felt its magnitude, and threw myself into realizing it. I couldn’t think of a nobler quest than the final eradication of involuntary death, and felt willing to spend the rest of my life trying to make it happen.

First I collected research on organic brain transplantation, on maintaining the brain’s homeostatic and regulatory mechanisms outside the body (or in this case without the body), on a host of prosthetic and robotic technologies (including sensory prosthesis and substitution), and on the work in Brain-Computer-Interface technologies that would eventually allow a given brain to control its new, non-biological body—essentially collecting the disparate mechanisms and technologies that would collectively converge to facilitate the creation of a fully cybernetic body to house the organic brain and keep it alive past the death of its homeostatic and regulatory organs.

I had by this point come across online literature on Artificial Neurons (ANs) and Artificial Neural Networks (ANNs), which are basically simplified mathematical models of neurons meant to process information in a way coarsely comparable to them. There was no mention in the literature of integrating them with existing neurons or for replacing existing neurons towards the objective of immortality ; their use was merely as an interesting approach to computation particularly optimal to certain situations. While artificial neurons can be run on general-purpose hardware (massively parallel architectures being the most efficient for ANNs, however), I had something more akin to neuromorphic hardware in mind (though I wasn’t aware of that just yet).

At its most fundamental level, Artificial Neurons need not even be physical at all. Their basic definition is a mathematical model roughly based on neuronal operation – and there is nothing precluding that model from existing solely on paper, with no actual computation going on. When I discovered them, I had thought that a given artificial neuron was a physically-embodied entity, rather than a software simulation. – i.e., an electronic device that operates in a way comparable to biological neurons.  Upon learning that they were mathematical models however, and that each AN needn’t be a separate entity from the rest of the ANs in a given AN Network, I saw no problem in designing them so as to be separate physical entities (which they needed to be in order to fit the purposes I had for them – namely, the gradual replacement of biological neurons with prosthetic functional equivalents). Each AN would be a software entity run on a piece of computational substrate, enclosed in a protective casing allowing it to co-exist with the biological neurons already in-place. The mathematical or informational outputs of the simulated neuron would be translated into biophysical, chemical, and electrical output by operatively connecting the simulation to an appropriate series of actuators (which could range from being as simple as producing electric fields or currents, to the release of chemical stores of neurotransmitters) and likewise a series of sensors to translate biophysical, chemical, and electrical properties into the mathematical or informational form they would need to be in to be accepted as input by the simulated AN.

Thus at this point I didn’t make a fundamental distinction between replicating the functions and operations of a neuron via physical embodiment (e.g., via physically embodied electrical, chemical, and/or electromechanical systems) or via virtual embodiment (usefully considered as 2nd-order embodiment, e.g., via a mathematical or computational model, whether simulation or emulation, run on a 1st-order physically embodied computational substrate).

The potential advantages, disadvantages, and categorical differences between these two approaches were still a few months away. When I discovered ANs, still thinking of them as physically embodied electronic devices rather than as mathematical or computational models, I hadn’t yet moved on to ways of preserving the organic brain itself so as to delay its organic death. Their utility in constituting a more permanent, durable, and readily repairable supplement for our biological neurons wasn’t yet apparent.

I initially saw their utility as being intelligence amplification, extension and modification through their integration with the existing biological brain. I realized that they were categorically different than Brain-Computer Interfaces (BCIs) and normative neural prosthesis for being able to become an integral and continuous part of our minds and personalities – or more properly the subjective, experiential parts of our minds. If they communicated with single neurons and interact with them on their own terms—if the two were operationally indistinct—then they could become a continuous part of us in a way that didn’t seem possible for normative BCI due to their fundamental operational dissimilarity with existing biological neural networks. I also collected research on the artificial synthesis and regeneration of biological neurons as an alternative to ANs. This approach would replace an aging or dying neuron with an artificially synthesized but still structurally and operationally biological neuron, so as to maintain the aging or dying neuron’s existing connections and relative location. I saw this procedure (i.e., adding artificial or artificially synthesized but still biological neurons to the existing neurons constituting our brains, not yet for the purposes of gradually replacing the brain but instead for the purpose of mental expansion and amplification) as not only allowing us to extend our existing functional and experiential modalities (e.g., making us smarter through an increase in synaptic density and connectivity, and an increase in the number of neurons in general) but even to create fundamentally new functional and experiential modalities that are categorically unimaginable to us now via the integration of wholly new Artificial Neural Networks embodying such new modalities. Note that I saw this as newly possible with my cybernetic-body approach because additional space could be made for the additional neurons and neural networks, whereas the degree with which we could integrate new, artificial neural networks in a normal biological body would be limited by the available volume of the unmodified skull.

Before I discovered ANs, I speculated in my notes as to whether the “bionic nerves” alluded to in some of the literature I had collected by this point (specifically regarding BCI, neural prosthesis, and the ability to operatively connect a robotic prosthetic extremity – e.g., an arm or a leg – via BCI) could be used to extend the total number of neurons and synaptic connections in the biological brain. This sprang from my knowledge on the operational similarities between neurons and muscle cells, both of the larger class of excitable cells.

Kurzweil’s cyborgification approach (i.e., that we could integrate non-biological systems with our biological brains to such an extent that the biological portions become so small as to be negligible to our subjective-continuity when they succumb to cell-death, thus achieving effective immortality without needing to actually replace any of our existing biological neurons at all) may have been implicit in this concept. I envisioned our brains increasing in size many times over and thus that the majority of our mind would be embodied or instantiated in larger part by the artificial portion than by the biological portions; the fact that the degree with which the loss of a part of our brain will affect our emergent personalities depends on how big (other potential metrics alternative to size include connectivity and the degree with which other systems depend on that potion for their own normative operation) that lost part is in comparison to the total size of the brain, the loss of a lobe being much worse than the loss of a neuron, follows naturally from this initial premise. The lack of any explicit statement of this realization in my notes during this period, however, makes this mere speculation.

It wasn’t until November 11, 2006, that I had the fundamental insight underlying mind-uploading—that the replacement of existing biological neurons with non-biological functional equivalents that maintain the existing relative location and connection of such biological neurons could very well facilitate maintaining the memory and personality embodied therein or instantiated thereby—essentially achieving potential technological immortality, since the approach is based on replacement and iterations of replacement-cycles can be run indefinitely. Moreover, the fact that we would be manufacturing such functional equivalents ourselves means that we could not only diagnose potential eventual dysfunctions easier and with greater speed, but we could manufacture them so as to have readily replaceable parts, thus simplifying the process of physically remediating any such potential dysfunction or operational degradation, even going so far as to include systems for the safe import and export of replacement components or as to make all such components readily detachable, so that we don’t have to cause damage to adjacent structures and systems in the process of removing a given component.

Perhaps it wasn’t so large a conceptual step from knowledge of the existence of computational models of neurons to the realization of using them to replace existing biological neurons towards the aim of immortality. Perhaps I take too much credit for independently conceiving both the underlying conceptual gestalt of mind-uploading, as well as some specific technologies and methodologies for its pragmatic technological implementation. Nonetheless, it was a realization I arrived at on my own, and was one that I felt would allow us to escape the biological death of the brain itself.

While I was aware (after a little more research) that ANNs were mathematical (and thus computational) models of neurons, hereafter referred to as the informationalist-functionalist approach, I felt that a physically embodied (i.e., not computationally emulated or simulated) prosthetic approach, hereafter referred to as the physicalist-functionalist approach, would be a better approach to take. This was because even if the brain were completely reducible to computation, a prosthetic approach would necessarily facilitate the computation underlying the functioning of the neuron (as the physical operations of biological neurons do presently), and if the brain proved to be computationally irreducible, then the prosthetic approach would in such a case presumably preserve whatever salient physical processes were necessary. So the prosthetic approach didn’t necessitate the computational-reducibility premise – but neither did it preclude such a view, thereby allowing me to hedge my bets and increase the cumulative likelihood of maintaining subjective-continuity of consciousness through substrate-replacement in general.

This marks a telling proclivity recurrent throughout my project: the development of mutually exclusive and methodologically and/or technologically alternate systems for a given objective, each based upon alternate premises and contingencies – a sort of possibilizational web unfurling fore and outward. After all, if one approach failed, then we had alternate approaches to try. This seemed like the work-ethic and conceptualizational methodology that would best ensure the eventual success of the project.

I also had less assurance in the sufficiency of the informational-functionalist approach at the time, stemming mainly from a misconception with the premises of normative Whole-Brain Emulation (WBE). When I first discovered ANs, I was more dubious at that point about the computational reducibility of the mind because I thought that it relied on the premise that neurons act in a computational fashion (i.e., like normative computational paradigms) to begin with—thus a conflation of classical computation with neural operation—rather than on the conclusion, drawn from the Church-Turing thesis, that mind is computable because the universe is. It is not that the brain is a computer to begin with, but that we can model any physical process via mathematical/computational emulation and simulation. The latter would be the correct view, and I didn’t really realize that this was the case until after I had discovered the WBE roadmap in 2010. This fundamental misconception allowed me, however, to also independently arrive at the insight underlying the real premise of WBE:  that combining premise A – that we had various mathematical computational models of neuron behavior – with premise B – that we can perform mathematical models on computers – ultimately yields the conclusion C – that we can simply perform the relevant mathematical models on computational substrate, thereby effectively instantiating the mind “embodied” in those neural operations while simultaneously eliminating many logistical and technological challenges to the prosthetic approach. This seemed both likelier than the original assumption—conflating neuronal activity with normative computation, as a special case not applicable to, say, muscle cells or skin cells, which wasn’t the presumption WBE makes at all—because this approach only required the ability to mathematically model anything, rather than relying on a fundamental equivalence between two different types of physical system (neuron and classical computer). The fact that I mistakenly saw it as an approach to emulation that was categorically dissimilar to normative WBE also helped urge me on to continue conceptual development of the various sub-aims of the project after having found that the idea of brain emulation already existed, because I thought that my approach was sufficiently different to warrant my continued effort.

There are other reasons for suspecting that mind may not be computationally reducible using current computational paradigms – reasons that rely on neither vitalism (i.e., the claim that mind is at least partially immaterial and irreducible to physical processes) nor on the invalidity of the Church-Turing thesis. This line of reasoning has nothing to do with functionality and everything to do with possible physical bases for subjective-continuity, both a) immediate subjective-continuity (i.e., how can we be a unified, continuous subjectivity if all our component parts are discrete and separate in space?), which can be considered as the capacity to have subjective experience, also called sentience (as opposed to sapience, which designated the higher cognitive capacities like abstract thinking) and b) temporal subjective-continuity (i.e., how do we survive as continuous subjectivities through a process of gradual substrate replacement?). Thus this argument impacts the possibility of computationally reproducing mind only insofar as the definition of mind is not strictly functional but is made to include a subjective sense of self—or immediate subjective-continuity. Note that subjective-continuity through gradual replacement is not speculative (just the scale and rate required to sufficiently implement it are), but rather has proof of concept in the normal metabolic replacement of the neuron’s constituent molecules. Each of us is a different person materially than we were 7 years ago, and we still claim to retain subjective-continuity. Thus, gradual replacement works; it is just the scale and rate required that are under question.

This is another way in which my approach and project differs from WBE. WBE equates functional equivalence (i.e., the same output via different processes) with subjective equivalence, whereas my approach involved developing variant approaches to neuron-replication-unit design that were each based on a different hypothetical basis for instantive subjective continuity.

 Are Current Computational Paradigms Sufficient?

Biological neurons are both analog and binary. It is useful to consider a 1st tier of analog processes, manifest in the action potentials occurring all over the neuronal soma and terminals, with a 2nd tier of binary processing, in that either the APs’ sum crosses the threshold value needed for the neuron to fire, or it falls short of it and the neuron fails to fire. Thus the analog processes form the basis of the digital ones. Moreover, the neuron is in an analog state even in the absence of membrane depolarization through the generation of the resting-membrane potential (maintained via active ion-transport proteins), which is analog rather than binary for always undergoing minor fluctuations due to it being an active process (ion-pumps) that instantiates it. Thus the neuron at any given time is always in the process of a state-transition (and minor state-transitions still within the variation-range allowed by a given higher-level static state; e.g., resting membrane potential is a single state, yet still undergoes minor fluctuations because the ions and components manifesting it still undergo state-transitions without the resting-membrane potential itself undergoing a state-transition), and thus is never definitively on or off. This brings us to the first potential physical basis for both immediate and temporal subjective-continuity. Analog states are continuous, and the fact that there is never a definitive break in the processes occurring at the lower levels of the neuron represents a potential basis for our subjective sense of immediate and temporal continuity.

Paradigms of digital computation, on the other hand, are at the lowest scale either definitively on or definitively off. While any voltage within a certain range will cause the generation of an output, it is still at base binary because in the absence of input the logic elements are not producing any sort of fluctuating voltage—they are definitively off. In binary computation, the substrates undergo a break (i.e., region of discontinuity) in their processing in the absence of inputs, and are in this way fundamentally dissimilar to the low-level operational modality of biological neurons by virtue of being procedurally discrete rather than procedurally continuous.

If the premise that the analog and procedurally continuous nature of neuron-functioning (including action potentials, resting-membrane potential, and metabolic processes that form a potential basis for immediate and temporal subjective-continuity) holds true, then current digital paradigms of computation may prove insufficient at maintaining subjective-continuity if used as the substrate in a gradual-replacement procedure, while still being sufficient to functionally replicate the mind in all empirically verifiable metrics and measures. This is due to both the operational modality of binary processing (i.e., lack of analog output) and the procedural modality of binary processing (the lack of temporal continuity or lack of producing minor fluctuations in reference to a baseline state when in a resting or inoperative state). A logic element could have a fluctuating resting voltage rather than the absence of any voltage and could thus be procedurally continuous while still being operationally discrete by producing solely binary outputs.

So there are two possibilities here. One is that any physical substrate used to replicate a neuron (whether via 1st-order embodiment a.k.a prosthesis/physical-systems, or via 2nd-order embodiment a.k.a computational emulation or simulation) must not undergo a break in its operation in the absence of input, because biological neurons do not, and this may be a potential basis for instantive subjective-continuity, but rather must produce a continuous or uninterrupted signal when in a “steady-state” (i.e., in the absence of inputs). The second possibility includes all the premises of the first, but adds that such an inoperative-state signal (or “no-inputs”-state signal) undergo minor fluctuations (because then a steady stream of causal interaction is occurring – e.g., producing a steady signal could be as discontinuous as no signal, like “being on pause”.

Thus one reason for developing the physicalist-functionalist (i.e., physically embodied prosthetic) approach to NRU design was a hedging of bets, in the case that a.) current computational substrates fail to replicate a personally continuous mind for the reasons described above, or b.) we fail to discover the principles underlying a given physical process—thus being unable to predictively model it—but still succeed in integrating them with the artificial systems comprising the prosthetic approach until such a time as to be able to discover their underlying principles, or c.) in the event that we find some other, heretofore unanticipated conceptual obstacle to computational reducibility of mind.

Franco Cortese is an editor for Transhumanity.net, as well as one of its most frequent contributors.  He has also published articles and essays on Immortal Life and The Rational Argumentator. He contributed 4 essays and 7 debate responses to the digital anthology Human Destiny is to Eliminate Death: Essays, Rants and Arguments About Immortality.

Franco is an Advisor for Lifeboat Foundation (on its Futurists Board and its Life Extension Board) and contributes regularly to its blog.

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