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Once upon a time, a powerful Sumerian king named Gilgamesh went on a quest, as such characters often do in these stories of myth and legend. Gilgamesh had witnessed the death of his best friend, Enkidu, and, fearing a similar fate, went in search of immortality. The great king failed to find the secret of eternal life but took solace that his deeds would live well beyond his mortal years.
Fast-forward four thousand years, give or take a century, and Gilgamesh (as famous as any B-list celebrity today, despite the passage of time) would probably be heartened to learn that many others have taken up his search for longevity. Today, though, instead of battling epic monsters and the machinations of fickle gods, those seeking to enhance and extend life are cutting-edge scientists and visionary entrepreneurs who are helping unlock the secrets of human biology.
Chief among them is Aubrey de Grey, a biomedical gerontologist who founded the SENS Research Foundation, a Silicon Valley-based research organization that seeks to advance the application of regenerative medicine to age-related diseases. SENS stands for Strategies for Engineered Negligible Senescence, a term coined by de Grey to describe a broad array (seven, to be precise) of medical interventions that attempt to repair or prevent different types of molecular and cellular damage that eventually lead to age-related diseases like cancer and Alzheimer’s.
Many of the strategies focus on senescent cells, which accumulate in tissues and organs as people age. Not quite dead, senescent cells stop dividing but are still metabolically active, spewing out all sorts of proteins and other molecules that can cause inflammation and other problems. In a young body, that’s usually not a problem (and probably part of general biological maintenance), as a healthy immune system can go to work to put out most fires.
However, as we age, senescent cells continue to accumulate, and at some point the immune system retires from fire watch. Welcome to old age.
Of Mice and Men
Researchers like de Grey believe that treating the cellular underpinnings of aging could not only prevent disease but significantly extend human lifespans. How long? Well, if you’re talking to de Grey, Biblical proportions—on the order of centuries.
De Grey says that science has made great strides toward that end in the last 15 years, such as the ability to copy mitochondrial DNA to the nucleus. Mitochondria serve as the power plant of the cell but are highly susceptible to mutations that lead to cellular degeneration. Copying the mitochondrial DNA into the nucleus would help protect it from damage.
Another achievement occurred about six years ago when scientists first figured out how to kill senescent cells. That discovery led to a spate of new experiments in mice indicating that removing these ticking-time-bomb cells prevented disease and even extended their lifespans. Now the anti-aging therapy is about to be tested in humans.
“As for the next few years, I think the stream of advances is likely to become a flood—once the first steps are made, things get progressively easier and faster,” de Grey tells Singularity Hub. “I think there’s a good chance that we will achieve really dramatic rejuvenation of mice within only six to eight years: maybe taking middle-aged mice and doubling their remaining lifespan, which is an order of magnitude more than can be done today.”
Not Horsing Around
Richard G.A. Faragher, a professor of biogerontology at the University of Brighton in the United Kingdom, recently made discoveries in the lab regarding the rejuvenation of senescent cells with chemical compounds found in foods like chocolate and red wine. He hopes to apply his findings to an animal model in the future—in this case,horses.
“We have been very fortunate in receiving some funding from an animal welfare charity to look at potential treatments for older horses,” he explains to Singularity Hub in an email. “I think this is a great idea. Many aspects of the physiology we are studying are common between horses and humans.”
What Faragher and his colleagues demonstrated in a paper published in BMC Cell Biology last year was that resveralogues, chemicals based on resveratrol, were able to reactivate a protein called a splicing factor that is involved in gene regulation. Within hours, the chemicals caused the cells to rejuvenate and start dividing like younger cells.
“If treatments work in our old pony systems, then I am sure they could be translated into clinical trials in humans,” Faragher says. “How long is purely a matter of money. Given suitable funding, I would hope to see a trial within five years.”
Show Them the Money
Faragher argues that the recent breakthroughs aren’t because a result of emerging technologies like artificial intelligence or the gene-editing tool CRISPR, but a paradigm shift in how scientists understand the underpinnings of cellular aging. Solving the “aging problem” isn’t a question of technology but of money, he says.
“Frankly, when AI and CRISPR have removed cystic fibrosis, Duchenne muscular dystrophy or Gaucher syndrome, I’ll be much more willing to hear tales of amazing progress. Go fix a single, highly penetrant genetic disease in the population using this flashy stuff and then we’ll talk,” he says. “My faith resides in the most potent technological development of all: money.”
De Grey is less flippant about the role that technology will play in the quest to defeat aging. AI, CRISPR, protein engineering, advances in stem cell therapies, and immune system engineering—all will have a part.
“There is not really anything distinctive about the ways in which these technologies will contribute,” he says. “What’s distinctive is that we will need all of these technologies, because there are so many different types of damage to repair and they each require different tricks.”
It’s in the Blood
A startup in the San Francisco Bay Area believes machines can play a big role in discovering the right combination of factors that lead to longer and healthier lives—and then develop drugs that exploit those findings.
BioAge Labs raised nearly $11 million last year for its machine learning platform that crunches big data sets to find blood factors, such as proteins or metabolites, that are tied to a person’s underlying biological age. The startup claims that these factors can predict how long a person will live.
“Our interest in this comes out of research into parabiosis, where joining the circulatory systems of old and young mice—so that they share the same blood—has been demonstrated to make old mice healthier and more robust,” Dr. Eric Morgen, chief medical officer at BioAge, tells Singularity Hub.
Based on that idea, he explains, it should be possible to alter those good or bad factors to produce a rejuvenating effect.
“Our main focus at BioAge is to identify these types of factors in our human cohort data, characterize the important molecular pathways they are involved in, and then drug those pathways,” he says. “This is a really hard problem, and we use machine learning to mine these complex datasets to determine which individual factors and molecular pathways best reflect biological age.”
Saving for the Future
Of course, there’s no telling when any of these anti-aging therapies will come to market. That’s why Forever Labs, a biotechnology startup out of Ann Arbor, Michigan, wants your stem cells now. The company offers a service to cryogenically freeze stem cells taken from bone marrow.
The theory behind the procedure, according to Forever Labs CEO Steven Clausnitzer, is based on research showing that stem cells may be a key component for repairing cellular damage. That’s because stem cells can develop into many different cell types and can divide endlessly to replenish other cells. Clausnitzer notes that there are upwards of a thousand clinical studies looking at using stem cells to treat age-related conditions such as cardiovascular disease.
However, stem cells come with their own expiration date, which usually coincides with the age that most people start experiencing serious health problems. Stem cells harvested from bone marrow at a younger age can potentially provide a therapeutic resource in the future.
“We believe strongly that by having access to your own best possible selves, you’re going to be well positioned to lead healthier, longer lives,” he tells Singularity Hub.
“There’s a compelling argument to be made that if you started to maintain the bone marrow population, the amount of nuclear cells in your bone marrow, and to re-up them so that they aren’t declining with age, it stands to reason that you could absolutely mitigate things like cardiovascular disease and stroke and Alzheimer’s,” he adds.
Clausnitzer notes that the stored stem cells can be used today in developing therapies to treat chronic conditions such as osteoarthritis. However, the more exciting prospect—and the reason he put his own 38-year-old stem cells on ice—is that he believes future stem cell therapies can help stave off the ravages of age-related disease.
“I can start reintroducing them not to treat age-related disease but to treat the decline in the stem-cell niche itself, so that I don’t ever get an age-related disease,” he says. “I don’t think that it equates to immortality, but it certainly is a step in that direction.”
Indecisive on Immortality
The societal implications of a longer-living human species are a guessing game at this point. We do know that by mid-century, the global population of those aged 65 and older will reach 1.6 billion, while those older than 80 will hit nearly 450 million, according to the National Academies of Science. If many of those people could enjoy healthy lives in their twilight years, an enormous medical cost could be avoided.
Faragher is certainly working toward a future where human health is ubiquitous. Human immortality is another question entirely.
“The longer lifespans become, the more heavily we may need to control birth rates and thus we may have fewer new minds. This could have a heavy ‘opportunity cost’ in terms of progress,” he says.
And does anyone truly want to live forever?
“There have been happy moments in my life but I have also suffered some traumatic disappointments. No [drug] will wash those experiences out of me,” Faragher says. “I no longer view my future with unqualified enthusiasm, and I do not think I am the only middle-aged man to feel that way. I don’t think it is an accident that so many ‘immortalists’ are young.
“They should be careful what they wish for.”
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It’s the end of a long day in your apartment in the early 2040s. You decide your work is done for the day, stand up from your desk, and yawn. “Time for a film!” you say. The house responds to your cues. The desk splits into hundreds of tiny pieces, which flow behind you and take on shape again as a couch. The computer screen you were working on flows up the wall and expands into a flat projection screen. You relax into the couch and, after a few seconds, a remote control surfaces from one of its arms.
In a few seconds flat, you’ve gone from a neatly-equipped office to a home cinema…all within the same four walls. Who needs more than one room?
This is the dream of those who work on “programmable matter.”
In his recent book about AI, Max Tegmark makes a distinction between three different levels of computational sophistication for organisms. Life 1.0 is single-celled organisms like bacteria; here, hardware is indistinguishable from software. The behavior of the bacteria is encoded into its DNA; it cannot learn new things.
Life 2.0 is where humans live on the spectrum. We are more or less stuck with our hardware, but we can change our software by choosing to learn different things, say, Spanish instead of Italian. Much like managing space on your smartphone, your brain’s hardware will allow you to download only a certain number of packages, but, at least theoretically, you can learn new behaviors without changing your underlying genetic code.
Life 3.0 marks a step-change from this: creatures that can change both their hardware and software in something like a feedback loop. This is what Tegmark views as a true artificial intelligence—one that can learn to change its own base code, leading to an explosion in intelligence. Perhaps, with CRISPR and other gene-editing techniques, we could be using our “software” to doctor our “hardware” before too long.
Programmable matter extends this analogy to the things in our world: what if your sofa could “learn” how to become a writing desk? What if, instead of a Swiss Army knife with dozens of tool attachments, you just had a single tool that “knew” how to become any other tool you could require, on command? In the crowded cities of the future, could houses be replaced by single, OmniRoom apartments? It would save space, and perhaps resources too.
Such are the dreams, anyway.
But when engineering and manufacturing individual gadgets is such a complex process, you can imagine that making stuff that can turn into many different items can be extremely complicated. Professor Skylar Tibbits at MIT referred to it as 4D printing in a TED Talk, and the website for his research group, the Self-Assembly Lab, excitedly claims, “We have also identified the key ingredients for self-assembly as a simple set of responsive building blocks, energy and interactions that can be designed within nearly every material and machining process available. Self-assembly promises to enable breakthroughs across many disciplines, from biology to material science, software, robotics, manufacturing, transportation, infrastructure, construction, the arts, and even space exploration.”
Naturally, their projects are still in the early stages, but the Self-Assembly Lab and others are genuinely exploring just the kind of science fiction applications we mooted.
For example, there’s the cell-phone self-assembly project, which brings to mind eerie, 24/7 factories where mobile phones assemble themselves from 3D printed kits without human or robotic intervention. Okay, so the phones they’re making are hardly going to fly off the shelves as fashion items, but if all you want is something that works, it could cut manufacturing costs substantially and automate even more of the process.
One of the major hurdles to overcome in making programmable matter a reality is choosing the right fundamental building blocks. There’s a very important balance to strike. To create fine details, you need to have things that aren’t too big, so as to keep your rearranged matter from being too lumpy. This might make the building blocks useless for certain applications—for example, if you wanted to make tools for fine manipulation. With big pieces, it might be difficult to simulate a range of textures. On the other hand, if the pieces are too small, different problems can arise.
Imagine a setup where each piece is a small robot. You have to contain the robot’s power source and its brain, or at least some kind of signal-generator and signal-processor, all in the same compact unit. Perhaps you can imagine that one might be able to simulate a range of textures and strengths by changing the strength of the “bond” between individual units—your desk might need to be a little bit more firm than your bed, which might be nicer with a little more give.
Early steps toward creating this kind of matter have been taken by those who are developing modular robots. There are plenty of different groups working on this, including MIT, Lausanne, and the University of Brussels.
In the latter configuration, one individual robot acts as a centralized decision-maker, referred to as the brain unit, but additional robots can autonomously join the brain unit as and when needed to change the shape and structure of the overall system. Although the system is only ten units at present, it’s a proof-of-concept that control can be orchestrated over a modular system of robots; perhaps in the future, smaller versions of the same thing could be the components of Stuff 3.0.
You can imagine that with machine learning algorithms, such swarms of robots might be able to negotiate obstacles and respond to a changing environment more easily than an individual robot (those of you with techno-fear may read “respond to a changing environment” and imagine a robot seamlessly rearranging itself to allow a bullet to pass straight through without harm).
Speaking of robotics, the form of an ideal robot has been a subject of much debate. In fact, one of the major recent robotics competitions—DARPA’s Robotics Challenge—was won by a robot that could adapt, beating Boston Dynamics’ infamous ATLAS humanoid with the simple addition of a wheel that allowed it to drive as well as walk.
Rather than building robots into a humanoid shape (only sometimes useful), allowing them to evolve and discover the ideal form for performing whatever you’ve tasked them to do could prove far more useful. This is particularly true in disaster response, where expensive robots can still be more valuable than humans, but conditions can be very unpredictable and adaptability is key.
Further afield, many futurists imagine “foglets” as the tiny nanobots that will be capable of constructing anything from raw materials, somewhat like the “Santa Claus machine.” But you don’t necessarily need anything quite so indistinguishable from magic to be useful. Programmable matter that can respond and adapt to its surroundings could be used in all kinds of industrial applications. How about a pipe that can strengthen or weaken at will, or divert its direction on command?
We’re some way off from being able to order our beds to turn into bicycles. As with many tech ideas, it may turn out that the traditional low-tech solution is far more practical and cost-effective, even as we can imagine alternatives. But as the march to put a chip in every conceivable object goes on, it seems certain that inanimate objects are about to get a lot more animated.
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The US Army recently announced that it is developing the first drones that can spot and target vehicles and people using artificial intelligence (AI). This is a big step forward. Whereas current military drones are still controlled by people, this new technology will decide who to kill with almost no human involvement. Continue reading