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

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The New Renaissance Hat
Franco Cortese
May 11, 2013
Recommend this page.
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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.

Chapter Two Bibliography

Copeland, J. B. (2008). Neural Network. In The Stanford Encyclopedia of Philosophy (Fall 2008 Edition). Retrieved February 28, 2013. from http://plato.stanford.edu/archives/fall2008/entries/church-turing

Crick, F. (1984 Nov 8-14). Memory and molecular turnover. In Nature, 312(5990)(101). PMID: 6504122

Criterion of Falsifiability, Encyclopædia Britannica. Encyclopædia Britannica Online Academic Edition. Retrieved February 28, 2013, from http://www.britannica.com/EBchecked/topic/201091/criterion-of-falsifiability

Drexler, K. E. (1986). Engines of Creation: The Coming Era of Nanotechnology. New York: Anchor Books.

Grabianowski (2007). How Brain-computer Interfaces Work. Retrieved February 28, 2013, from http://computer.howstuffworks.com/brain-computer-interface.htm

Koene, R. (2011). The Society of Neural Prosthetics and Whole Brain Emulation Science. Retrieved February 28, 2013, from http://www.minduploading.org/

Martins, N. R., Erlhagen, W. & Freitas Jr., R. A. (2012). Non-destructive whole-brain monitoring using nanorobots: Neural electrical data rate requirements. International Journal of Machine Consciousness, 2011. Retrieved February 28, 2013, from http://www.nanomedicine.com/Papers/NanoroboticBrainMonitoring2012.pdf.

Narayan, A. (2004). Computational Methods for NEMS. Retrieved February 28, 2013, from http://nanohub.org/resources/407.

Sandberg, A. & Bostrom, N. (2008). Whole Brain Emulation: A Roadmap, Technical Report #2008-3. Retrieved February 28, 2013, from Whole Brain Emulation: A Roadmap, Technical Report #2008-3.

Star, E. N., Kwiatkowski, D. J. & Murthy, V. N. (2002). Rapid turnover of actin in dendritic spines and its regulation by activity. Nature Neuroscience, 5 , 239-246.

Tsien, J. Z., Rampon, C., Tang,Y.P. & Shimizu, E. (2000). NMDA receptor dependent synaptic reinforcement as a crucial process for memory consolidation. Science, 290 , 1170-1174.

Vladimir, Z. (2013). Neural Network. In Encyclopædia Britannica Online Academic Edition. Retrieved February 28, 2013, from http://www.britannica.com/EBchecked/topic/410549/neural-network

Wolf, W. & (March 2009). Cyber-physical Systems. In Embedded Computing. Retrieved February 28, 2013, from http://www.jiafuwan.net/download/cyber_physical_systems.pdf

 

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Private or Governmental Funding for Indefinite Life Extension? – Post by G. Stolyarov II

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Categories: Politics, Science, Transhumanism, Tags: , , , , , , , , , , , , , ,

The New Renaissance Hat
G. Stolyarov II
March 27, 2013
Recommend this page.
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I was recently asked to comment on an Immortal Life debate/discussion thread about whether governmental or private approaches to funding and motivating research on indefinite life extension are best.

Mine is definitely a libertarian view. I do not support advocating for government funding for life extension, unless the funding is combined with larger reductions in military spending or other destructive government spending. I discuss this issue in two of my videos:

- Eliminating Death – Part 18 – Never Seek Government Funding

- Libertarian Life-Extension Reforms – #6 – Medical Research Instead of Military Spending

The danger of government funding of life extension is that it comes with many political strings attached, and may lead life-extension research itself to be shackled by politically influential opponents of technological progress.

The great weakness of politics as a strategy is that it requires consensus among elites and some connection to majority approval, as well as the overcoming of numerous bureaucratic hurdles and obsolete habits. Private action, as long as it is lawful, can simply be pursued irrespective of how many people agree. There is thus much more flexibility and potential for quick deployment with private approaches toward radical life extension.

Private investment into life-extension research can occur in many ways, both for-profit and non-profit, both direct and indirect. Seasteading is indeed a highly promising approach for experimenting with novel medicines and therapies that might take over a decade to be approved by the FDA in the United States or similar “screening” agencies in other countries.

At the same time, Tom Mooney is correct about the need for a grassroots education campaign. By the time radical life extension begins to become a reality, there needs to be a strong current of public opinion supporting it. Otherwise, the “bioconservatives” might just manage to obtain enough support for their agenda to thwart this vital progress.

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The Breakthrough Prize in Life Sciences: Turning the Tide for Life Extension – Video by G. Stolyarov II

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Categories: Business, Science, Technology, Transhumanism, Tags: , , , , , , , , , , , , , , , ,

The tide of funding for life-extension research has turned. With the announcement of the Breakthrough Prize in Life Sciences – sponsored by such renowned entrepreneurs as Yuri Milner, Sergei Brin, and Mark Zuckerberg, as well as Zuckerberg’s wife Priscilla Chan and Anne Wojcicki of 23andMe – there is now a world-class mechanism for rewarding outstanding scientists whose work contributes to understanding and curing debilitating diseases and extending human life. Mr. Stolyarov explains the incentives that the Breakthrough Prize creates for cutting-edge life-extension research and a more meritocratic society.

Remember to LIKE, FAVORITE, and SHARE this video in order to spread rational discourse on this issue.

Support these video-creation efforts by donating here and here.

References
- “The Breakthrough Prize in Life Sciences: Turning the Tide for Life Extension” – Essay by G. Stolyarov II -
- Article on Transhumanity.net
- Breakthrough Prize in Life Sciences Website
- List of first 11 laureates of the Breakthrough Prize
- “Mark Zuckerberg, Sergey Brin, Yuri Milner Create $33 Million Breakthrough Prize For Medical Research” – Addy Dugdale – Fast Company – February 20, 2013
- “Breakthrough Prize announced by Silicon Valley entrepreneurs” – Rory Carroll – The Guardian
- “Bill Gates Wants to Be Immortal” – Adam Clark Estes – Motherboard

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Computer Games, Distributed Computing, and Life Extension – Video by G. Stolyarov II

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Categories: Science, Technology, Transhumanism, Tags: , , , , , , , , , , , , , , , , , , , , , ,

Imagine if it were possible to help cure disease and lengthen human lifespans simply by playing one’s computer games of choice. Here, Mr. Stolyarov describes a concept for doing just that, and he welcomes efforts from any of you to help bring it about.

Remember to LIKE, FAVORITE, and SHARE this video in order to spread rational discourse on this issue.

Support these video-creation efforts by donating here and here.

References
- “Computer Games, Distributed Computing, and Life Extension” – Article by G. Stolyarov II – The Rational Argumentator
- Article and discussion on Transhumanity.net
- Mr. Stolyarov’s Page of Distributed Computing Statistics
- Rosetta@home
- Folding@home
- World Community Grid
- Human Proteome Folding
- Help Conquer Cancer
- FoldIt
- “Public Solves Protein Structure” – Jef Akst – The Scientist – September 18, 2011
- “ALS Cause and Protein-Folding Prediction – Thoughts on Two Impressive Scientific Discoveries ” – Video by G. Stolyarov II – September 20, 2011

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Computer Games, Distributed Computing, and Life Extension – Article by G. Stolyarov II

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Categories: Science, Technology, Transhumanism, Tags: , , , , , , , , , , , , , , , , , , , , , ,

The New Renaissance Hat
G. Stolyarov II
February 26, 2013
Recommend this page.
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Imagine if it were possible to help cure disease and lengthen human lifespans simply by playing one’s computer games of choice. Here, I describe a concept for doing just that, and I welcome efforts from any readers to help bring it about.

To make a practical, concrete difference in accelerating the advent of radical human life extension, one of the most powerful contributions a layman (non-biologist, non-doctor, non-engineer) can make is to donate idle computer time to distributed computing projects focused on biomedical research. Immensely promising distributed computing endeavors include Rosetta@home, Folding@home, and World Community Grid’s Human Proteome Folding and Help Conquer Cancer projects.  I am a major participant in many of these projects. (I rank in the 98.6th percentile for all distributed computing users by total credit and in the 99.5th percentile by recent average credit.) My computer runs these projects almost nonstop, and I have even made several upgrades, partly to enhance my contribution.  Distributed computing enables scientific research to occur at rates and scales previously inconceivable. Researchers utilize thousands of computers worldwide to perform incredible numbers of complex calculations that they could not have processed in their labs alone.

Billions of computers now exist, and it seems so easy to just download a distributed computing client and let it run while the computer is idle. The computer owner does not need to be technically knowledgeable about the field of research in order to make a positive and direct contribution. Yet participation in distributed computing projects is still orders of magnitude below where it should be. For instance, as of February 23, 2013, Folding@home has 1,674,431 all-time donors of computer resources; the front page suggests that 167,833 computers are currently active in the project. Rosetta@home has 355,661 total donors, while World Community Grid has 401,270. The number of people worldwide who care about advancing medical research is surely far larger than this.

 Yet even an easy task like installing a distributed computing client may be beyond the comfort zone of many people with busy, often hectic, lives. If these people take time out of their day for activities not related to their primary occupations, they will do so because they find those activities entertaining, relaxing, or both. Computer games are an immensely popular example; they directly engage hundreds of millions of people worldwide for hundreds of billions of hours every year. If this level of contribution were made to distributed computing projects, we would see the pace of research accelerate tenfold or more.

There is already one game, FoldIt, that attempts to utilize human creativity to directly address one challenge related to life extension: the prediction of protein-folding configurations. FoldIt’s users have even had some success where computer algorithms have not. However, FoldIt’s gameplay is not for everyone, just like any particular genre of computer game will attract some enthusiastic users but will leave others indifferent.

To radically increase the use of distributed computing, I recommend a new approach: the design of computer games that automatically run distributed computing projects in the background when they are played. Players would not need to acquire the game with the purpose of contributing to research projects; their primary motivation should be to enjoy the game. However, one of the marketing points in the game’s favor could be that it would enable people to make a meaningful contribution to research while they enjoyed themselves. Such games would not need to be related to the subject of the research at all; they could be about absolutely anything, and there could be numerous games of this sort made to appeal to a wide variety of consumer demographics. Indeed, creators of existing games could work on ways to link them to distributed computing clients and use this to emphasize their companies’ philanthropic side.

Each game could include an option to activate the distributed computing client even if the game is not being played. In this way, players who come to enjoy their participation in distributed computing projects could extend that participation beyond their gaming sessions. On the other hand, a lot of players would acquire the game just to play it, while being only peripherally aware of the distributed computing aspect. However, their consent to the distributed computing would be a part of the usage agreement associated with the game. They would contribute to important biomedical research by default, just like all of us contribute to the carbon dioxide available to the Earth’s plants simply by exhaling.

I am not a programmer myself, but I strongly encourage any programmer and/or game developer reading this article to develop this proposed connection between any game and a distributed computing project. This concept should be in the public domain, and, to the extent this is possible under current law, I hereby release any original ideas or concepts in this article into the public domain in full. I seek no monetary profit or even credit from such undertakings (though I would be extremely happy to be informed of efforts to implement them). I will benefit considerably if the implementation of this idea radically accelerates life-extension research, and this benefit would certainly be enough for me.  It is in my best interest for numerous parallel, competing, or collaborative efforts to arise in this area, and for many people to try variations on this idea.

I also welcome input from those who can anticipate some of the technical details and challenges of developing games of this sort. For instance, I would be interested in insights regarding the potential ease or difficulty of integrating a distributed computing client with another program. At present, I anticipate that most of the challenges would be technical, rather than legal, since BOINC, one of the most popular clients, is free software released under a GNU Lesser General Public License. My strong recommendation is for any efforts in this area to have an open-source character, welcoming contributions from all parties in order to make the vast benefits of this project realizable. At least some of the games created as a result could be made freely downloadable, so as to entice more people into obtaining them with nothing to lose.

The idea is now out there. I urge you to help make it happen in any way you are able.

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The Breakthrough Prize in Life Sciences: Turning the Tide for Life Extension – Article by G. Stolyarov II

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Categories: Business, Science, Technology, Transhumanism, Tags: , , , , , , , , , , , , , , , ,

The New Renaissance Hat
G. Stolyarov II
February 23, 2013
Recommend this page.
******************************

The tide of funding for life-extension research has turned. With the announcement of the Breakthrough Prize in Life Sciences – sponsored by such renowned entrepreneurs as Yuri Milner, Sergei Brin, and Mark Zuckerberg, as well as Zuckerberg’s wife Priscilla Chan and Anne Wojcicki of 23andMe – there is now a world-class mechanism for rewarding outstanding scientists whose work contributes to understanding and curing debilitating diseases and extending human life. (You can find out more about this prize from The Guardian and Fast Company.) The first eleven laureates of the prize have already been selected, and every subsequent year eleven more will receive $3 million each.

The incentives behind the Breakthrough Prize are exactly right. In short, they move our society ever closer to a meritocracy. By receiving a sizable fortune, each scientist – still at the top of his or her career – would no longer need to worry about finances. He or she would at last have a justly deserved reward for ingenious work that advances the struggle of human civilization against disease, decay, and death. To produce ground-breaking research in biology, medicine, and biotechnology requires a kind of passion that does not get extinguished just because one’s day-to-day material needs have been satisfied. By getting the material worries out of the way, that passion is allowed full and free rein. Innovation becomes the dominant motive force of further projects, and further research and breakthroughs can proceed without fear of running out of funding.

The people funding the prize are themselves excellent exemplars of meritocracy. They became wealthy by their own efforts – not through inheritance, political pull, or expropriation of others, but through providing services that millions of people voluntarily sought out and recognized as enhancing their lives. It is not surprising that these entrepreneurs of merit would seek to reward the merit in others – particularly merit that, through its further exercise, can eventually save the lives of us all, from the wealthiest to the poorest. The ideal of a societal meritocracy is one in which personal wealth is directly proportional to earned achievement. Meritocracy does not require central planning, because people of merit will naturally seek to exchange values and reward one another on a free market – provided that central planners do not distort the incentives toward doing so. The distribution of wealth will, over time, approach a purely meritocratic one solely as a result of such enlightened and free interactions. Of course, we are far from having a pure meritocracy today, for the incentives are significantly distorted by special political favors, barriers to entry, and the cultural corruption they engender. However, given the slightest opening, the meritocratic ideal will gradually penetrate into an ever-expanding array of endeavors. By the accident of history, computer and internet technologies have been some of the least centrally controlled in the 20th and early 21st centuries. The result was the emergence of a group of merit-based entrepreneurs who could use their wealth to fund productive benefactors of humankind in other fields.

Another ubiquitously known member of the larger group of merit-based achievers is Bill Gates, who has recently expressed his personal desire not to die during a Reddit AMA.  This makes perfect sense: a man who has everything that wealth in today’s world can provide, and who leads a happy and fulfilling life besides, must still confront the fundamental injustice of his personal demise – an injustice that the wealthiest among us have not been able to rectify, yet. While Bill Gates is not sponsoring the Breakthrough Prize (at least not at present), his philanthropic efforts are already going a long way toward alleviating many life-shortening diseases in the less-developed parts of the world. We can all hope that, over time, he and others like him will devote increasing shares of their wealth toward overcoming the more formidable barriers of biological senescence.

For now, the Breakthrough Prize in Life Sciences is an excellent start. It will raise the profile of life-extension research and inspire others to pursue ambitious projects in hopes of earning the prize. Unlike the Nobel Prize, which scientists earn many decades after their most prominent achievements, this prize will come much sooner to those whose transformational work strikes blows against some our least tractable adversaries. With the accelerating pace of technological progress, it only makes sense not to wait over a generation before recognizing their accomplishments. Not only the recipients, but also their benefactors – Milner, Brin, Zuckerberg, Chan, and Wojcicki – are to be saluted for giving a critical and ongoing boost to life-extension efforts on many fronts.

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Illiberal Belief #9: It’s a Small World – Article by Bradley Doucet

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The New Renaissance Hat
Bradley Doucet
January 11, 2013
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We have only one planet, it’s true, and there are ever more of us crowding onto its surface. With six billion humans and counting, surely we must be running out of land—if not on which to live, then on which to grow the enormous amounts of food required to feed us all. As evidence, we are reminded of the large swaths of the planet mired in poverty, a tragedy that is used to justify any number of illiberal policies, from Maoist one-child population control laws to Stalinist food rationing meant to stretch out our meagre and dwindling resources.

Thankfully, these fears are unjustified. The advent and improvement of air travel and modern communications technologies have certainly made the planet seem smaller—we can zip to the Far East in a matter of hours, or send electronic documents anywhere in the world in a matter of seconds—but it’s still the same gigantic ball of rock it has always been. The Earth is really staggeringly large; too large, in fact, to grasp intuitively. Of course, six billion is also too large a number to grasp intuitively. Only mathematics can help us understand if we are truly running out of space.

Our planet has a surface area of approximately 510 million square kilometres, of which just under 30% (149 million sq. km) is land area. How many people can the Earth support? According to Scientific American, “With current farming techniques, a little less than half an acre can grow enough food to feed one person.” One square kilometre contains roughly 247 acres, and so can feed approximately 500 people. If all of the land on Earth were suitable for food production, our planet could therefore support a population of some 73.5 billion people (149 million times 500). Of course, not all land is suitable for agriculture, but thankfully we don’t need it to be. Our current population of six billion could be fed on just 12 million square kilometres of agricultural land, an area slightly larger than the United States. Even at nine billion people (the downwardly-revised population peak we are set to hit by 2050)(1), we would only need 18 million square kilometres, representing just 12% of the land on Earth, or an area about the size of Russia. Furthermore, this figure assumes unrealistically that no further improvements in farming techniques will be invented over the next five decades.

1. Although it is true that there are more of us than ever, the 2004 UN projections show that population growth is slowing and total population is on course to top out at around nine billion by mid-century, far fewer than previously thought.
Bradley Doucet is Le Quebecois Libré‘s English Editor. A writer living in Montreal, he has studied philosophy and economics, and is currently completing a novel on the pursuit of happiness. He also writes for The New Individualist, an Objectivist magazine published by The Atlas Society, and sings.

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Philosophy Lives – Contra Stephen Hawking – Video by G. Stolyarov II

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Mr. Stolyarov’s refutation of Stephen Hawking’s statement that “philosophy is dead.”

In his 2010 book The Grand Design, cosmologist and theoretical physicist Stephen Hawking writes that science has displaced philosophy in the enterprise of discovering truth. While I have great respect for Hawking both in his capacities as a physicist and in his personal qualities — his advocacy of technological progress and his determination and drive to achieve in spite of his debilitating illness — the assertion that the physical sciences can wholly replace philosophy is mistaken. Not only is philosophy able to address questions outside the scope of the physical sciences, but the coherence and validity of scientific approaches itself rests on a philosophical foundation that was not always taken for granted — and still is not in many circles.

References
- “Philosophy Lives – Contra Stephen Hawking” – Essay by G. Stolyarov II
- “The Grand Design (book)” – Wikipedia
- “Stephen Hawking” – Wikipedia

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Philosophy Lives – Contra Stephen Hawking – Article by G. Stolyarov II

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Categories: Philosophy, Science, Transhumanism, Tags: , , , , , , , , , , , , , , , , , , , , , , , , , ,

The New Renaissance Hat
G. Stolyarov II
January 1, 2013
Recommend this page.
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In his 2010 book The Grand Design, cosmologist and theoretical physicist Stephen Hawking writes that science has displaced philosophy in the enterprise of discovering truth. While I have great respect for Hawking both in his capacities as a physicist and in his personal qualities – his advocacy of technological progress and his determination and drive to achieve in spite of his debilitating illness – the assertion that the physical sciences can wholly replace philosophy is mistaken. Not only is philosophy able to address questions outside the scope of the physical sciences, but the coherence and validity of scientific approaches itself rests on a philosophical foundation that was not always taken for granted – and still is not in many circles.

Hawking writes, “Living in this vast world that is by turns kind and cruel, and gazing at the immense heavens above, people have always asked a multitude of questions: How can we understand the world in which we find ourselves? How does the universe behave? What is the nature of reality? Where did all this come from? Did the universe need a creator? Most of us do not spend most of our time worrying about these questions, but almost all of us worry about them some of the time. Traditionally these are questions for philosophy, but philosophy is dead. Philosophy has not kept up with modern developments in science, particularly physics. Scientists have become the bearers of the torch of discovery in our quest for knowledge.”

I hesitate to speculate why Hawking considers philosophy to be “dead” – but perhaps this view partly arises from frustration at the non-reality-oriented teachings of many postmodernist philosophers who still prevail in many academic and journalistic circles. Surely, those who deny the comprehensibility of reality and allege that it is entirely a societal construction do not aid in the quest for discovery and understanding of what really exists. Likewise, our knowledge cannot be enhanced by those who deny that there exist systematic and specific methods that are graspable by human reason and that can be harnessed for the purposes of discovery. It is saddening indeed that prominent philosophical figures have embraced anti-realist positions in metaphysics and anti-rational, anti-empirical positions in epistemology. Physicists, in their everyday practice, necessarily rely on external observational evidence and on logical deductions from the empirical data. In this way, and to the extent that they provide valid explanations of natural phenomena, they are surely more reality-oriented than most postmodernist philosophers. Yet philosophy does not need to be this way – and, indeed, philosophical schools of thought throughout history and in the present day are not only compatible with the scientific approach to reality, but indispensable to it.

Contrary to the pronouncements of prominent postmodernists, a venerable strain of thought – dating back to at least Aristotle and extending all the way to today’s transhumanists, Objectivists, and natural-law thinkers – holds that an objective reality exists, that it can be understood through systematic observation and reason, and that its understanding should be pursued by all of us. This is the philosophical strain responsible for the accomplishments of Classical Antiquity and the progress made during the Renaissance, the Enlightenment, the Industrial Revolution, and the Information Revolution. While such philosophy is not the same as the physical sciences, the physical sciences rely on it to the extent that they embrace the approach known as the scientific method, which itself rests on philosophical premises. These premises include the existence of an external reality independent of the wishes and imagination of any observer, the existence of a definite identity of any given entity at any given time, the reliance on identical conditions producing identical outcomes, the principles of causation and non-contradiction, and the ability of human beings to systematically alter outcomes in the physical world by understanding its workings and modifying physical systems accordingly. This latter principle – that, in Francis Bacon’s words, “Nature, to be commanded, must be obeyed” – was the starting point for the Scientific Revolution of the 17th Century, which inaugurated subsequent massive advances in technology, standards of living, and human understanding of the universe.  Even those scientists who do not acknowledge or explicitly reject the importance of philosophy nonetheless implicitly rely on these premises in the very conduct of their scientific work – to the extent that such work accurately describes reality. These premises are not the only ones possible – but they are the only ones that are fully right. Alternatives – including reliance on alleged supernatural revelation, wishful thinking, and unconditional deference to authority – have been tried time and again, only to result in stagnation and mental traps that prevented substantive improvements to the human condition.

But there is more. Not only are the physical sciences without a foundation if philosophy is to be ignored, but the very reason for pursuing them remains unaddressed without the branch of philosophy that focuses on what we ought to do: ethics. Contrary to those who would posit an insurmountable “is-ought” gap, ethics can indeed be derived from the facts of reality, but not solely by the tools of physics, chemistry, biology, or any others of the “hard” physical sciences. An additional element is required: the fact that we ourselves exist as rational, conscious beings, who are capable of introspection and of analysis of external data. From the physical sciences we can derive ways to sustain and improve our material well-being – sometimes our very survival. But only ethics can tell us that we ought to pursue such survival – a conclusion we reach through introspection and logical reasoning. No experiment, no test is needed to tell us that we ought to keep living. This conclusion arises as antecedent to a consistent pursuit of any action at all; to achieve any goal, we must be alive. To pursue death, the opposite of life, contradicts the very notion of acting, which has life as a prerequisite.  Once we have accepted that premise, an entire system of logical deductions follows with regard to how we ought to approach the external world – the pursuit of knowledge, interactions with others, improvement of living conditions, protection against danger. The physical sciences can provide many of the empirical data and regularities needed to assess alternative ways of living and to develop optimal solutions to human challenges. But ethics is needed to keep the goals of scientific study in mind. The goals should ultimately relate to ways to enhance human well-being. If the pursuit of human well-being – consistent with the imperative of each individual to continue living – is abandoned, then the physical sciences alone cannot provide adequate guidance. Indeed, they can be utilized to produce horrors – as the development of nuclear weapons in the 20th century exemplified. Geopolitical considerations of coercive power and nationalism were permitted to overshadow humanistic considerations of life and peace, and hundreds of thousands of innocents perished due to a massive government-sponsored science project, while the fate of human civilization hung in the balance for over four decades.

The questions cited by Hawking are indeed philosophical questions, at least in part. Aspects of these questions, while they are broadly reliant on the existence of an objective reality, do not require specific experiments to answer. Rather, like many of the everyday questions of our existence, they rely only on the ubiquitous inputs of our day-to-day experience, generalized within our minds and formulated as starting premises for a logical deductive process. The question “How can we understand the world in which we find ourselves?“ has different answers based on the realm of focus and endeavor. Are we looking to understand the function of a mechanism, or the origin of a star? Different tools are required for each, but systematic experimentation and observation would be required in each case. This is an opening for the physical sciences and the scientific method. There are, however, ubiquitous observations about our everyday world that can be used as inputs into our decision-making – a process we engage in regularly as we navigate a room, eat a meal, engage in conversation or deliberation, or transport any object whatsoever. Simply as a byproduct of routine living, these observations provide us with ample data for a series of logical deductions and inferences which do not strictly belong to any scientific branch, even though specific parts of our world could be better understood from closer scientific observation.

The question “How does the universe behave?” actually arises in part from a philosophical presupposition that “the universe” is a single entity with any sort of coordinated behavior whatsoever. An alternative view – which I hold – is that the word “universe” is simply convenient mental shorthand for describing the totality of every single entity that exists, in lieu of actually enumerating them all. Thus, while each entity has its own definite nature, “the universe” may not have a single nature or behavior. Perhaps a more accurate framing of that question would be, “What attributes or behaviors are common to all entities that exist?” To answer that question, a combination of ubiquitous observation and scientific experimentation is required. Ubiquitous observation tells us that all entities are material, but only scientific experimentation can tell us what the “building blocks” of matter are. Philosophy alone cannot recommend any model of the atom or of subatomic particles, among multiple competing non-contradictory models. Philosophy can, however, rightly serve to check the logical coherence of any particular model and to reject erroneous interpretations of data which produce internally contradictory answers. Such rejection does not mean that the data are inaccurate, or even that a particular scientific theory cannot predict the behavior of entities – but rather that any verbal understanding of the accurate data and predictive models should also be consistent with logic, causation, and everyday human experience. At the very least, if a coherent verbal understanding is beyond our best efforts at present, philosophy should be vigilant against the promulgation of incoherent verbal understandings. It is better to leave certain scientific models as systems of mathematical equations, uncommented on, than to posit evidently false interpretations that undermine laypeople’s view of the validity of our very existence and reasoning.

After all – to return to the ethical purpose of science – one major goal of scientific inquiry is to understand and explain the world we live in and experience on a daily basis. If any scientific model is said to result in the conclusion that our world does not ‘really’ exist or that our entire experience is illusory (rather than just occasional quirks in our biology, such as those which produce optical illusions, misleading us, in an avoidable manner, under specific unusual circumstances), then it is the philosophical articulation of that model that is flawed. The model itself may be retained in another form – such as mathematical notation – that can be used to predict and study phenomena which continue to defy verbal understanding, with the hope that someday a satisfactory verbal understanding will be attained. Without this philosophic vigilance, scientific breakthroughs may be abused by charlatans for the purpose of misleading people into ruining their lives. As a prominent example of this, multiple strains of mysticism have arisen out of bad philosophical interpretations of quantum mechanics – for instance, the belief, articulated in such pseudo-self-help books as The Secret, that people can mold reality with their thoughts alone and that, instead of working hard and thinking rationally, they can become immensely wealthy and cure themselves of cancer just by wanting it enough. Without a rigorous philosophical defense of reason and objective reality, either by scientists themselves or by their philosopher allies, this mystical nonsense will render scientific enterprises increasingly misunderstood by and isolated from large segments of the public, who will become increasingly superstitious, anti-intellectual, and reliant on wishful thinking.

The question “What is the nature of reality?” is a partly philosophical and partly scientific one. The philosophical dimension – metaphysics – is needed to posit that an objective, understandable reality exists at all. The scientific dimension comes into play in comprehending specific real entities, from stars to biological organisms – relying on the axioms and derivations of metaphysics for the experimental study of such entities to even make sense or promise to produce reliable results. Philosophy cannot tell you what the biological structure of a given organism is like, but it can tell you that there is one, and that praying or wishing really hard to understand it will not reveal its identity to you. Philosophy can also tell you that, in the absence of external conditions that would dramatically affect that biological structure, it will not magically change into a dramatically different structure.

The questions “Where did all this come from? Did the universe need a creator?” are scientific only to a point. When exploring the origin of a particular planet or star – or of life on Earth – they are perfectly amenable to experimentation and to extrapolation from historical evidence. Hence, the birth of the solar system, abiogenesis, and biological evolution are all appropriate subjects of study for the hard sciences. Moreover, scientific study can address the question of whether a particular object needed to have a creator and can, for instance, conclude that a mechanical watch needed to have a watchmaker, but no analogous maker needed to exist to bring about the structure of a complex biological organism. However, if the question arises as to whether existence itself had an origin or needed a creator, this is a matter for philosophy. Indeed, rational philosophy can point out the contradiction in the view that existence itself could ever not have existed, or that a creator outside of existence (and, by definition, non-existent at that time) could have brought existence into being.

Interestingly enough, Hawking comes to a similar conclusion – that cosmological history can be understood by a model that not include a sentient creator. I am glad that Hawking holds this view, but this specific conclusion does not require theoretical or experimental physics to validate; it simply requires a coherent understanding of terms such as “existence”, “universe”, and “creator”. Causation and non-contradiction both preclude the possibility of any ex nihilo creation. As for the question of whether there exist beings capable of vast cosmic manipulations and even the design of life forms – that is an empirical matter. Perhaps someday such beings will be discovered; perhaps someday humans will themselves become such beings through mastery of science and technology. The first steps have already been taken – for instance, with Craig Venter’s design of a synthetic living bacterium. Ethics suggests to me that this mastery of life is a worthwhile goal and that its proponents – transhumanists – should work to persuade those philosophers and laypeople who disagree.

More constructive dialogue between rational scientists and rational philosophers is in order, for the benefit of both disciplines. Philosophy can serve as a check on erroneous verbal interpretations of scientific discoveries, as well as an ethical guide for the beneficial application of those discoveries. Science can serve to provide observations and regularities which assist in the achievement of philosophically motivated goals. Furthermore, science can serve to disconfirm erroneous philosophical positions, in cases where philosophy ventures too far into specific empirical predictions which experimentation and targeted observation might falsify. To advance such fruitful interactions, it is certainly not productive to proclaim that one discipline or another is “dead”. I will be the first to admit that contemporary philosophy, especially of the kind that enjoys high academic prestige, is badly in need of reform. But such reform is only possible after widespread acknowledgment that philosophy does have a legitimate and significant role, and that it can do a much better job in fulfilling it.

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A Speculative Order of Arrival for Important Rejuvenation Therapies – Article by Reason

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The New Renaissance Hat
Reason
October 6, 2012
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A toolkit for producing true rejuvenation in humans will require a range of different therapies, each of which can repair or reverse one of the varied root causes of degenerative aging. Research is underway for all of these classes of therapy, but very slowly and with very little funding in some cases. The funding situation spans the gamut from that of the stem cell research community, where researchers are afloat in money and interest, to the search for ways to break down advanced glycation endproducts (AGEs), which is a funding desert by comparison, little known or appreciated outside the small scientific community that works in that field.

While bearing in mind that progress in projects with little funding is unpredictable in comparison to that of well-funded projects, I think that we can still take a stab at a likely order of arrival for various important therapies needed to reverse aging. Thus an incomplete list follows, running from the earliest to the latest arrival, with the caveat that it is based on the present funding and publicity situation. If any one of the weakly funded and unappreciated lines of research suddenly became popular and awash with resources, it would probably move up in the ordering:

1) Destruction of Senescent Cells

Destroying specific cells without harming surrounding cells is a well-funded line of research thanks to the cancer community, and the technology platforms under development can be adapted to target any type of cell once it is understood how to target its distinctive features.

The research community has already demonstrated benefits from senescent cell destruction, and there are research groups working on this problem from a number of angles. A method of targeting senescent cells for destruction was recently published, and we can expect to see more diverse attempts at this in the next few years. As soon as one of these can be shown to produce benefits in mice that are similar to the early demonstrations, then senescent cell clearance becomes a going concern: something to be lifted from the deadlocked US regulatory process and hopefully developed quickly into a therapy in Asia, accessed via medical tourism.

2) Selective Pruning and Support of the Immune System

One of the reasons for immune system decline is crowding out of useful immune cells by memory immune cells that serve little useful purpose. Here, targeted cell destruction can also produce benefits, and early technology demonstrations support this view. Again, the vital component is the array of mechanisms needed to target the various forms of immune cell that must be pruned. I expect the same rising tide of technology and knowledge that enables senescent cell targeting will lead to the arrival of immune cell targeting on much the same schedule.

Culling the immune system will likely have to be supported with some form of repopulation of cells. It is already possible to repopulate a patient’s immune system with immune cells cultivated from their own tissues, as demonstrated by the limited number of full immune system reboots carried out to cure autoimmune disorders. Alternatives to this process include some form of tissue engineering to recreate the dynamic, youthful thymus as a source of immune cells – or more adventurous processes such as cultivating thymic cells in a patient’s lymph nodes.

3) Mitochondrial Repair

Our mitochondria sabotage us. There’s a flaw in their structure and operation that causes a small but steadily increasing fraction of our cells to descend into a malfunctioning state that is destructive to bodily tissues and systems.

There are any number of proposed methods for dealing with this component of the aging process – either repairing or making it irrelevant – and a couple are in that precarious state of being just a little more solidity and work away from the point at which they could begin clinical development. The diversity of potential approaches in increasing too. Practical methods are now showing up for ways to put new mitochondria into cells, or target arbitrary therapies to the interior or mitochondria. It all looks very promising.

Further, the study of mitochondria is very broad and energetic, and has a strong presence in many areas of medicine and life science research. While few groups in the field are currently engaged in work on mitochondrial repair, there is an enormous reservoir of potential funding and workers awaiting any method of repair shown to produce solid results.

4) Reversing Stem Cell Aging

The stem cell research field is on a collision course with the issue of stem cell aging. Most of the medical conditions that are best suited to regenerative medicine, tissue engineering, and similar cell based therapies are age-related, and thus most of the patients are old. In order for therapies to work well, there must be ways to work around the issues caused by the aged biochemistry of the patient. To achieve this end, the research community will essentially have to enumerate the mechanisms by which stem cell populations decline and fail with age, and then reverse their effects.

Where stem cells themselves are damaged by age, stem cell populations will have to be replaced. This is already possible for many different types of stem cell, but there are potentially hundreds of different types of adult stem cell – and it is too much to expect for the processes and biochemistry to be very similar in all cases. A great deal of work will remain to be accomplished here even after the first triumphs involving hearts, livers, and kidneys.

Much of the problem, however, is not the stem cells but rather the environment they operate within. This is the bigger challenge: picking out all the threads of signalling, epigenetic change, and cause and effect that leads to quieted and diminished stem cell populations – and the resulting frailty as tissues are increasingly poorly supported. This is a fair sized task, and little more than inroads have been made to date – a few demonstrations in which one stem cell type has been coerced into acting with youthful vigor, and a range of research on possible processes and mechanisms to explain how an aging metabolism causes stem cells to slow down and stop their work.

The stem cell research community is, however, one of the largest in the world, and very well funded. This is a problem that they have to solve on the way to their declared goals. What I would expect to see here is for a range of intermediary stopgap solutions to emerge in the laboratory and early trials over the next decade. These will be limited ways to invigorate a few aged stem cell populations, intended to be used to boost the effectiveness of stem cell therapies for diseases of aging.

Any more complete or comprehensive solution for stem cell aging seems like a longer-term prospect, given that it involves many different stem cell populations with very different characteristics.

5) Clearing Advanced Glycation Endproducts (AGEs)

AGEs cause inflammation and other sorts of mischief through their presence, and this builds up with age. Unfortunately, research on breaking down AGEs to remove their contribution to degenerative aging has been a very thin thread indeed over the past few decades: next to no-one works on it, despite its importance, and very little funding is devoted to this research.

Now on the one hand it seems to be the case that one particular type of AGE – glucosepane – makes up 90% or more the AGEs in human tissues. On the other hand, efforts to find a safe way to break it down haven’t made any progress in the past decade, though a new initiative was launched comparatively recently. This is an excellent example of how minimally funded research can be frustrating: a field can hover just that one, single advance away from largely solving a major problem for years on end. All it takes is the one breakthrough, but the chances of that occurring depend heavily on the resources put into the problem: how many parallel lines of investigation can be followed, how many researchers are working away at it.

This is an excellent candidate for a line of research that could move upward in the order of arrival if either a large source of funding emerged or a plausible compound was demonstrated to safely and aggressively break down glucospane in cell cultures. There is far less work to be done here than to reverse stem cell aging, for example.

6) Clearing Aggregates and Lysomal Garbage

All sorts of aggregates build up within and around cells as a result of normal metabolic processes, causing harm as they grow, and the sheer variety of these waste byproducts is the real challenge. They range from the amyloid that features prominently in Alzheimer’s disease through to the many constituents of lipofuscin that clog up lysosomes and degrade cellular housekeeping processes. At this point in the advance of biotechnology it remains the case that dealing with each of the many forms of harmful aggregate must be its own project, and so there is a great deal of work involved in moving from where we stand today to a situation in which even a majority of the aggregates that build up with age can be removed.

The most promising lines of research to remove aggregates are immunotherapy, in which the immune system is trained or given the tools to to consume and destroy a particular aggregate, and medical bioremediation, which is the search for bacterial enzymes that can be repurposed as drugs to break down aggregates within cells. Immunotherapy to attack amyloid as a treatment for Alzheimer’s is a going concern, for example. Biomedical remediation is a younger and far less funded endeavor, however.

My expectation here is that some viable therapies for some forms of unwanted and harmful metabolic byproducts will emerge in the laboratory over the next decade, but that will prove to be just the start on a long road indeed. From here it’s hard for me to guess at where the 80/20 point might be in clearing aggregates: successfully clearing the five most common different compounds? Or the ten most common? Or twenty? Lipofuscin alone has dozens of different constituent chemicals and proteins, never mind the various other forms of aggregate involved in specific diseases such as Alzheimer’s.

But work is work: it can be surmounted. Pertinently, and again, the dominant issue in timing here is the lack of funding and support for biomedical remediation and similar approaches to clearing aggregates.

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.  

This work is reproduced here in accord with a Creative Commons Attribution license.  It was originally published on FightAging.org.

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