The Future is… Worms: Life Extension and Computer-Simulations

genetic_circuitPost-mortality is considered by most to be an intrinsic part of the so-called Technological Singularity. For centuries, improvements in medicine, nutrition and health have led to improved life expectancy. And in an age where so much more is possible – thanks to cybernetics, bio, nano, and medical advances – it stands to reason that people will alter their physique in order slow the onset of age and extend their lives even more.

And as research continues, new and exciting finds are being made that would seem to indicate that this future may be just around the corner. And at the heart of it may be a series of experiments involving worms. At the Buck Institute for Research and Aging in California, researchers have been tweaking longevity-related genes in nematode worms in order to amplify their lifespans.

immortal_wormsAnd the latest results caught even the researchers by surprise. By triggering mutations in two pathways known for lifespan extension – mutations that inhibit key molecules involved in insulin signaling (IIS) and the nutrient signaling pathway Target of Rapamycin (TOR) – they created an unexpected feedback effect that amplified the lifespan of the worms by a factor of five.

Ordinarily, a tweak to the TOR pathway results in a 30% lifespan extension in C. Elegans worms, while mutations in IIS (Daf-2) results in a doubling of lifespan. By combining the mutations, the researchers were expecting something around a 130% extension to lifespan. Instead, the worms lived the equivalent of about 400 to 500 human years.

antiagingAs Doctor Pankaj Kapahi said in an official statement:

Instead, what we have here is a synergistic five-fold increase in lifespan. The two mutations set off a positive feedback loop in specific tissues that amplified lifespan. These results now show that combining mutants can lead to radical lifespan extension — at least in simple organisms like the nematode worm.

The positive feedback loop, say the researchers, originates in the germline tissue of worms – a sequence of reproductive cells that may be passed onto successive generations. This may be where the interactions between the two mutations are integrated; and if correct, might apply to the pathways of more complex organisms. Towards that end, Kapahi and his team are looking to perform similar experiments in mice.

DNA_antiagingBut long-term, Kapahi says that a similar technique could be used to produce therapies for aging in humans. It’s unlikely that it would result in the dramatic increase to lifespan seen in worms, but it could be significant nonetheless. For example, the research could help explain why scientists are having a difficult time identifying single genes responsible for the long lives experienced by human centenarians:

In the early years, cancer researchers focused on mutations in single genes, but then it became apparent that different mutations in a class of genes were driving the disease process. The same thing is likely happening in aging. It’s quite probable that interactions between genes are critical in those fortunate enough to live very long, healthy lives.

A second worm-related story comes from the OpenWorm project, an international open source project dedicated to the creation of a bottom-up computer model of a millimeter-sized nemotode. As one of the simplest known multicellular life forms on Earth, it is considered a natural starting point for creating computer-simulated models of organic beings.

openworm-nematode-roundworm-simulation-artificial-lifeIn an important step forward, OpenWorm researchers have completed the simulation of the nematode’s 959 cells, 302 neurons, and 95 muscle cells and their worm is wriggling around in fine form. However, despite this basic simplicity, the nematode is not without without its share of complex behaviors, such as feeding, reproducing, and avoiding being eaten.

To model the complex behavior of this organism, the OpenWorm collaboration (which began in May 2013) is developing a bottom-up description. This involves making models of the individual worm cells and their interactions, based on their observed functionality in the real-world nematodes. Their hope is that realistic behavior will emerge if the individual cells act on each other as they do in the real organism.

openworm-nematode-roundworm-simulation-artificial-life-0Fortunately, we know a lot about these nematodes. The complete cellular structure is known, as well as rather comprehensive information concerning the behavior of the thing in reaction to its environment. Included in our knowledge is the complete connectome, a comprehensive map of neural connections (synapses) in the worm’s nervous system.

The big question is, assuming that the behavior of the simulated worms continues to agree with the real thing, at what stage might it be reasonable to call it a living organism? The usual definition of living organisms is behavioral, that they extract usable energy from their environment, maintain homeostasis, possess a capacity to grow, respond to stimuli, reproduce, and adapt to their environment in successive generations.

openworm-nematode1If the simulation exhibits these behaviors, combined with realistic responses to its external environment, should we consider it to be alive? And just as importantly, what tests would be considered to test such a hypothesis? One possibility is an altered version of the Turing test – Alan Turing’s proposed idea for testing whether or not a computer could be called sentient.

In the Turing test, a computer is considered sentient and sapient if it can simulate the responses of a conscious sentient being so that an auditor can’t tell the difference. A modified Turing test might say that a simulated organism is alive if a skeptical biologist cannot, after thorough study of the simulation, identify a behavior that argues against the organism being alive.

openworm-nematode2And of course, this raises an even larger questions. For one, is humanity on the verge of creating “artificial life”? And what, if anything, does that really look like? Could it just as easily be in the form of computer simulations as anthropomorphic robots and biomachinery? And if the answer to any of these questions is yes, then what exactly does that say about our preconceived notions about what life is?

If humanity is indeed moving into an age of “artificial life”, and from several different directions, it is probably time that we figure out what differentiates the living from the nonliving. Structure? Behavior? DNA? Local reduction of entropy? The good news is that we don’t have to answer that question right away. Chances are, we wouldn’t be able to at any rate.

Brain-ScanAnd though it might not seem apparent, there is a connection between the former and latter story here. In addition to being able to prolong life through genetic engineering, the ability to simulate consciousness through computer-generated constructs might just prove a way to cheat death in the future. If complex life forms and connectomes (like that involved in the human brain) can be simulated, then people may be able to transfer their neural patterns before death and live on in simulated form indefinitely.

So… anti-aging, artificial life forms, and the potential for living indefinitely. And to think that it all begins with the simplest multicellular life form on Earth – the nemotode worm. But then again, all life – nay, all of existence – depends upon the most simple of interactions, which in turn give rise to more complex behaviors and organisms. Where else would we expect the next leap in biotechnological evolution to come from?

And in the meantime, be sure to enjoy this video of the OpenWorm’s simulated nemotode in action


Sources:
IO9, cell.com, gizmag, openworm

Immortality Inc: Google’s “Calico”

calico-header-640x353Google has always been famous for investing in speculative ventures and future trends. Between their robot cars, Google Glass, the development of AI (the Google Brain), high-speed travel (the Hyperloop), and alternative energy, their seems to be no limit to what Musk and Page’s company will take on. And now, with Calico, Google has made the burgeoning industry of life-extension its business.

The newly formed company has set itself to “focus on health and well-being, in particular the challenge of aging and associated diseases.” Those were the words of Google co-founder Larry Page, who issued a two-part press release back in September. From this, it is known that Calico will focus on life extension and improvement. But in what way and with what business model, the company has yet to explain.

DNA-1What does seem clear at this point is that Art Levinson, the chairman of Apple and former CEO of Genentech (a pioneer in biotech) will be the one to head up this new venture. His history working his way from a research scientist on up to CEO of Genentech makes him the natural choice, since he will bring medical connections and credibility to a company that’s currently low on both.

Google Health, the company’s last foray into the health industry, was a failure for the company. This site, which began in 2008 and shut down in 2011, was a personal health information centralization service that allowed Google users to volunteer their health records. Once entered, the site would provide them with a merged health record, information on conditions, and possible interactions between drugs, conditions, and allergies.

Larry_PageIn addition, the reasons for the company’s venture into the realm of health and aging may have something to do with Larry Page’s own recent health concerns. For years, Page has struggled with vocal nerve strain, which led him to make a significant donation to research into the problem. But clearly, Calico aims to go beyond simple health problems and cures for known diseases.

google.cover.inddIn a comment to Time Magazine, Page stated that a cure for cancer would only extent the average human lifespan by 3 years. They want to think bigger than that, which could mean addressing the actual causes of aging, the molecular processes that break down cells. Given that Google Ventures included life extension technology as part of their recent bid to attract engineering students, Google’s top brass might have a slightly different idea.

And while this might all sound a bit farfetched, the concept of life-extension and even clinical immortality have been serious pursuits for some time. We tend to think of aging as a fact of life, something that is as inevitable as it is irreversible. However, a number of plausible scenarios have already been discussed that could slow or even end this process, ranging from genetic manipulation, nanotechnology, implant technology, and cellular therapy.

Fountain_of_Eternal_Life_cropWhether or not Calico will get into any of these fields remains to be seen. But keeping in mind that this is the company that has proposed setting aside land for no-hold barred experimentation and even talked about building a Space Elevator with a straight face. I wouldn’t be surprised if they started building cryogentic tanks and jars for preserving disembodies brains before long!

Source: extremetech.com, (2), content.time.com