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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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New planets found in distant corners of the galaxy. Climate models that may improve our understanding of sea level rise. The emergence of new antimalarial drugs. These scientific advances and discoveries have been in the news in recent months.
While representing wildly divergent disciplines, from astronomy to biotechnology, they all have one thing in common: Artificial intelligence played a key role in their scientific discovery.
One of the more recent and famous examples came out of NASA at the end of 2017. The US space agency had announced an eighth planet discovered in the Kepler-90 system. Scientists had trained a neural network—a computer with a “brain” modeled on the human mind—to re-examine data from Kepler, a space-borne telescope with a four-year mission to seek out new life and new civilizations. Or, more precisely, to find habitable planets where life might just exist.
The researchers trained the artificial neural network on a set of 15,000 previously vetted signals until it could identify true planets and false positives 96 percent of the time. It then went to work on weaker signals from nearly 700 star systems with known planets.
The machine detected Kepler 90i—a hot, rocky planet that orbits its sun about every two Earth weeks—through a nearly imperceptible change in brightness captured when a planet passes a star. It also found a sixth Earth-sized planet in the Kepler-80 system.
AI Handles Big Data
The application of AI to science is being driven by three great advances in technology, according to Ross King from the Manchester Institute of Biotechnology at the University of Manchester, leader of a team that developed an artificially intelligent “scientist” called Eve.
Those three advances include much faster computers, big datasets, and improved AI methods, King said. “These advances increasingly give AI superhuman reasoning abilities,” he told Singularity Hub by email.
AI systems can flawlessly remember vast numbers of facts and extract information effortlessly from millions of scientific papers, not to mention exhibit flawless logical reasoning and near-optimal probabilistic reasoning, King says.
AI systems also beat humans when it comes to dealing with huge, diverse amounts of data.
That’s partly what attracted a team of glaciologists to turn to machine learning to untangle the factors involved in how heat from Earth’s interior might influence the ice sheet that blankets Greenland.
Algorithms juggled 22 geologic variables—such as bedrock topography, crustal thickness, magnetic anomalies, rock types, and proximity to features like trenches, ridges, young rifts, and volcanoes—to predict geothermal heat flux under the ice sheet throughout Greenland.
The machine learning model, for example, predicts elevated heat flux upstream of Jakobshavn Glacier, the fastest-moving glacier in the world.
“The major advantage is that we can incorporate so many different types of data,” explains Leigh Stearns, associate professor of geology at Kansas University, whose research takes her to the polar regions to understand how and why Earth’s great ice sheets are changing, questions directly related to future sea level rise.
“All of the other models just rely on one parameter to determine heat flux, but the [machine learning] approach incorporates all of them,” Stearns told Singularity Hub in an email. “Interestingly, we found that there is not just one parameter…that determines the heat flux, but a combination of many factors.”
The research was published last month in Geophysical Research Letters.
Stearns says her team hopes to apply high-powered machine learning to characterize glacier behavior over both short and long-term timescales, thanks to the large amounts of data that she and others have collected over the last 20 years.
Emergence of Robot Scientists
While Stearns sees machine learning as another tool to augment her research, King believes artificial intelligence can play a much bigger role in scientific discoveries in the future.
“I am interested in developing AI systems that autonomously do science—robot scientists,” he said. Such systems, King explained, would automatically originate hypotheses to explain observations, devise experiments to test those hypotheses, physically run the experiments using laboratory robotics, and even interpret the results. The conclusions would then influence the next cycle of hypotheses and experiments.
His AI scientist Eve recently helped researchers discover that triclosan, an ingredient commonly found in toothpaste, could be used as an antimalarial drug against certain strains that have developed a resistance to other common drug therapies. The research was published in the journal Scientific Reports.
Automation using artificial intelligence for drug discovery has become a growing area of research, as the machines can work orders of magnitude faster than any human. AI is also being applied in related areas, such as synthetic biology for the rapid design and manufacture of microorganisms for industrial uses.
King argues that machines are better suited to unravel the complexities of biological systems, with even the most “simple” organisms are host to thousands of genes, proteins, and small molecules that interact in complicated ways.
“Robot scientists and semi-automated AI tools are essential for the future of biology, as there are simply not enough human biologists to do the necessary work,” he said.
Creating Shockwaves in Science
The use of machine learning, neural networks, and other AI methods can often get better results in a fraction of the time it would normally take to crunch data.
For instance, scientists at the National Center for Supercomputing Applications, located at the University of Illinois at Urbana-Champaign, have a deep learning system for the rapid detection and characterization of gravitational waves. Gravitational waves are disturbances in spacetime, emanating from big, high-energy cosmic events, such as the massive explosion of a star known as a supernova. The “Holy Grail” of this type of research is to detect gravitational waves from the Big Bang.
Dubbed Deep Filtering, the method allows real-time processing of data from LIGO, a gravitational wave observatory comprised of two enormous laser interferometers located thousands of miles apart in California and Louisiana. The research was published in Physics Letters B. You can watch a trippy visualization of the results below.
In a more down-to-earth example, scientists published a paper last month in Science Advances on the development of a neural network called ConvNetQuake to detect and locate minor earthquakes from ground motion measurements called seismograms.
ConvNetQuake uncovered 17 times more earthquakes than traditional methods. Scientists say the new method is particularly useful in monitoring small-scale seismic activity, which has become more frequent, possibly due to fracking activities that involve injecting wastewater deep underground. You can learn more about ConvNetQuake in this video:
King says he believes that in the long term there will be no limit to what AI can accomplish in science. He and his team, including Eve, are currently working on developing cancer therapies under a grant from DARPA.
“Robot scientists are getting smarter and smarter; human scientists are not,” he says. “Indeed, there is arguably a case that human scientists are less good. I don’t see any scientist alive today of the stature of a Newton or Einstein—despite the vast number of living scientists. The Physics Nobel [laureate] Frank Wilczek is on record as saying (10 years ago) that in 100 years’ time the best physicist will be a machine. I agree.”
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Move over, deep learning. Neuromorphic computing—the next big thing in artificial intelligence—is on fire.
Just last week, two studies individually unveiled computer chips modeled after information processing in the human brain.
The first, published in Nature Materials, found a perfect solution to deal with unpredictability at synapses—the gap between two neurons that transmit and store information. The second, published in Science Advances, further amped up the system’s computational power, filling synapses with nanoclusters of supermagnetic material to bolster information encoding.
The result? Brain-like hardware systems that compute faster—and more efficiently—than the human brain.
“Ultimately we want a chip as big as a fingernail to replace one big supercomputer,” said Dr. Jeehwan Kim, who led the first study at MIT in Cambridge, Massachusetts.
Experts are hopeful.
“The field’s full of hype, and it’s nice to see quality work presented in an objective way,” said Dr. Carver Mead, an engineer at the California Institute of Technology in Pasadena not involved in the work.
Software to Hardware
The human brain is the ultimate computational wizard. With roughly 100 billion neurons densely packed into the size of a small football, the brain can deftly handle complex computation at lightning speed using very little energy.
AI experts have taken note. The past few years saw brain-inspired algorithms that can identify faces, falsify voices, and play a variety of games at—and often above—human capability.
But software is only part of the equation. Our current computers, with their transistors and binary digital systems, aren’t equipped to run these powerful algorithms.
That’s where neuromorphic computing comes in. The idea is simple: fabricate a computer chip that mimics the brain at the hardware level. Here, data is both processed and stored within the chip in an analog manner. Each artificial synapse can accumulate and integrate small bits of information from multiple sources and fire only when it reaches a threshold—much like its biological counterpart.
Experts believe the speed and efficiency gains will be enormous.
For one, the chips will no longer have to transfer data between the central processing unit (CPU) and storage blocks, which wastes both time and energy. For another, like biological neural networks, neuromorphic devices can support neurons that run millions of streams of parallel computation.
Optimism aside, reproducing the biological synapse in hardware form hasn’t been as easy as anticipated.
Neuromorphic chips exist in many forms, but often look like a nanoscale metal sandwich. The “bread” pieces are generally made of conductive plates surrounding a switching medium—a conductive material of sorts that acts like the gap in a biological synapse.
When a voltage is applied, as in the case of data input, ions move within the switching medium, which then creates conductive streams to stimulate the downstream plate. This change in conductivity mimics the way biological neurons change their “weight,” or the strength of connectivity between two adjacent neurons.
But so far, neuromorphic synapses have been rather unpredictable. According to Kim, that’s because the switching medium is often comprised of material that can’t channel ions to exact locations on the downstream plate.
“Once you apply some voltage to represent some data with your artificial neuron, you have to erase and be able to write it again in the exact same way,” explains Kim. “But in an amorphous solid, when you write again, the ions go in different directions because there are lots of defects.”
In his new study, Kim and colleagues swapped the jelly-like switching medium for silicon, a material with only a single line of defects that acts like a channel to guide ions.
The chip starts with a thin wafer of silicon etched with a honeycomb-like pattern. On top is a layer of silicon germanium—something often present in transistors—in the same pattern. This creates a funnel-like dislocation, a kind of Grand Canal that perfectly shuttles ions across the artificial synapse.
The researchers then made a neuromorphic chip containing these synapses and shot an electrical zap through them. Incredibly, the synapses’ response varied by only four percent—much higher than any neuromorphic device made with an amorphous switching medium.
In a computer simulation, the team built a multi-layer artificial neural network using parameters measured from their device. After tens of thousands of training examples, their neural network correctly recognized samples 95 percent of the time, just 2 percent lower than state-of-the-art software algorithms.
The upside? The neuromorphic chip requires much less space than the hardware that runs deep learning algorithms. Forget supercomputers—these chips could one day run complex computations right on our handheld devices.
A Magnetic Boost
Meanwhile, in Boulder, Colorado, Dr. Michael Schneider at the National Institute of Standards and Technology also realized that the standard switching medium had to go.
“There must be a better way to do this, because nature has figured out a better way to do this,” he says.
His solution? Nanoclusters of magnetic manganese.
Schneider’s chip contained two slices of superconducting electrodes made out of niobium, which channel electricity with no resistance. When researchers applied different magnetic fields to the synapse, they could control the alignment of the manganese “filling.”
The switch gave the chip a double boost. For one, by aligning the switching medium, the team could predict the ion flow and boost uniformity. For another, the magnetic manganese itself adds computational power. The chip can now encode data in both the level of electrical input and the direction of the magnetisms without bulking up the synapse.
It seriously worked. At one billion times per second, the chips fired several orders of magnitude faster than human neurons. Plus, the chips required just one ten-thousandth of the energy used by their biological counterparts, all the while synthesizing input from nine different sources in an analog manner.
The Road Ahead
These studies show that we may be nearing a benchmark where artificial synapses match—or even outperform—their human inspiration.
But to Dr. Steven Furber, an expert in neuromorphic computing, we still have a ways before the chips go mainstream.
Many of the special materials used in these chips require specific temperatures, he says. Magnetic manganese chips, for example, require temperatures around absolute zero to operate, meaning they come with the need for giant cooling tanks filled with liquid helium—obviously not practical for everyday use.
Another is scalability. Millions of synapses are necessary before a neuromorphic device can be used to tackle everyday problems such as facial recognition. So far, no deal.
But these problems may in fact be a driving force for the entire field. Intense competition could push teams into exploring different ideas and solutions to similar problems, much like these two studies.
If so, future chips may come in diverse flavors. Similar to our vast array of deep learning algorithms and operating systems, the computer chips of the future may also vary depending on specific requirements and needs.
It is worth developing as many different technological approaches as possible, says Furber, especially as neuroscientists increasingly understand what makes our biological synapses—the ultimate inspiration—so amazingly efficient.
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