Tag Archives: 2015
#435474 Watch China’s New Hybrid AI Chip Power ...
When I lived in Beijing back in the 90s, a man walking his bike was nothing to look at. But today, I did a serious double-take at a video of a bike walking his man.
No kidding.
The bike itself looks overloaded but otherwise completely normal. Underneath its simplicity, however, is a hybrid computer chip that combines brain-inspired circuits with machine learning processes into a computing behemoth. Thanks to its smart chip, the bike self-balances as it gingerly rolls down a paved track before smoothly gaining speed into a jogging pace while navigating dexterously around obstacles. It can even respond to simple voice commands such as “speed up,” “left,” or “straight.”
Far from a circus trick, the bike is a real-world demo of the AI community’s latest attempt at fashioning specialized hardware to keep up with the challenges of machine learning algorithms. The Tianjic (天机*) chip isn’t just your standard neuromorphic chip. Rather, it has the architecture of a brain-like chip, but can also run deep learning algorithms—a match made in heaven that basically mashes together neuro-inspired hardware and software.
The study shows that China is readily nipping at the heels of Google, Facebook, NVIDIA, and other tech behemoths investing in developing new AI chip designs—hell, with billions in government investment it may have already had a head start. A sweeping AI plan from 2017 looks to catch up with the US on AI technology and application by 2020. By 2030, China’s aiming to be the global leader—and a champion for building general AI that matches humans in intellectual competence.
The country’s ambition is reflected in the team’s parting words.
“Our study is expected to stimulate AGI [artificial general intelligence] development by paving the way to more generalized hardware platforms,” said the authors, led by Dr. Luping Shi at Tsinghua University.
A Hardware Conundrum
Shi’s autonomous bike isn’t the first robotic two-wheeler. Back in 2015, the famed research nonprofit SRI International in Menlo Park, California teamed up with Yamaha to engineer MOTOBOT, a humanoid robot capable of driving a motorcycle. Powered by state-of-the-art robotic hardware and machine learning, MOTOBOT eventually raced MotoGPTM world champion Valentino Rossi in a nail-biting match-off.
However, the technological core of MOTOBOT and Shi’s bike vastly differ, and that difference reflects two pathways towards more powerful AI. One, exemplified by MOTOBOT, is software—developing brain-like algorithms with increasingly efficient architecture, efficacy, and speed. That sounds great, but deep neural nets demand so many computational resources that general-purpose chips can’t keep up.
As Shi told China Science Daily: “CPUs and other chips are driven by miniaturization technologies based on physics. Transistors might shrink to nanoscale-level in 10, 20 years. But what then?” As more transistors are squeezed onto these chips, efficient cooling becomes a limiting factor in computational speed. Tax them too much, and they melt.
For AI processes to continue, we need better hardware. An increasingly popular idea is to build neuromorphic chips, which resemble the brain from the ground up. IBM’s TrueNorth, for example, contains a massively parallel architecture nothing like the traditional Von Neumann structure of classic CPUs and GPUs. Similar to biological brains, TrueNorth’s memory is stored within “synapses” between physical “neurons” etched onto the chip, which dramatically cuts down on energy consumption.
But even these chips are limited. Because computation is tethered to hardware architecture, most chips resemble just one specific type of brain-inspired network called spiking neural networks (SNNs). Without doubt, neuromorphic chips are highly efficient setups with dynamics similar to biological networks. They also don’t play nicely with deep learning and other software-based AI.
Brain-AI Hybrid Core
Shi’s new Tianjic chip brought the two incompatibilities together onto a single piece of brainy hardware.
First was to bridge the deep learning and SNN divide. The two have very different computation philosophies and memory organizations, the team said. The biggest difference, however, is that artificial neural networks transform multidimensional data—image pixels, for example—into a single, continuous, multi-bit 0 and 1 stream. In contrast, neurons in SNNs activate using something called “binary spikes” that code for specific activation events in time.
Confused? Yeah, it’s hard to wrap my head around it too. That’s because SNNs act very similarly to our neural networks and nothing like computers. A particular neuron needs to generate an electrical signal (a “spike”) large enough to transfer down to the next one; little blips in signals don’t count. The way they transmit data also heavily depends on how they’re connected, or the network topology. The takeaway: SNNs work pretty differently than deep learning.
Shi’s team first recreated this firing quirk in the language of computers—0s and 1s—so that the coding mechanism would become compatible with deep learning algorithms. They then carefully aligned the step-by-step building blocks of the two models, which allowed them to tease out similarities into a common ground to further build on. “On the basis of this unified abstraction, we built a cross-paradigm neuron scheme,” they said.
In general, the design allowed both computational approaches to share the synapses, where neurons connect and store data, and the dendrites, the outgoing branches of the neurons. In contrast, the neuron body, where signals integrate, was left reconfigurable for each type of computation, as were the input branches. Each building block was combined into a single unified functional core (FCore), which acts like a deep learning/SNN converter depending on its specific setup. Translation: the chip can do both types of previously incompatible computation.
The Chip
Using nanoscale fabrication, the team arranged 156 FCores, containing roughly 40,000 neurons and 10 million synapses, onto a chip less than a fifth of an inch in length and width. Initial tests showcased the chip’s versatility, in that it can run both SNNs and deep learning algorithms such as the popular convolutional neural network (CNNs) often used in machine vision.
Compared to IBM TrueNorth, the density of Tianjic’s cores increased by 20 percent, speeding up performance ten times and increasing bandwidth at least 100-fold, the team said. When pitted against GPUs, the current hardware darling of machine learning, the chip increased processing throughput up to 100 times, while using just a sliver (1/10,000) of energy.
Although these stats are great, real-life performance is even better as a demo. Here’s where the authors gave their Tianjic brain a body. The team combined one chip with multiple specialized networks to process vision, balance, voice commands, and decision-making in real time. Object detection and target tracking, for example, relied on a deep neural net CNN, whereas voice commands and balance data were recognized using an SNN. The inputs were then integrated inside a neural state machine, which churned out decisions to downstream output modules—for example, controlling the handle bar to turn left.
Thanks to the chip’s brain-like architecture and bilingual ability, Tianjic “allowed all of the neural network models to operate in parallel and realized seamless communication across the models,” the team said. The result is an autonomous bike that rolls after its human, balances across speed bumps, avoids crashing into roadblocks, and answers to voice commands.
General AI?
“It’s a wonderful demonstration and quite impressive,” said the editorial team at Nature, which published the study on its cover last week.
However, they cautioned, when comparing Tianjic with state-of-the-art chips designed for a single problem toe-to-toe on that particular problem, Tianjic falls behind. But building these jack-of-all-trades hybrid chips is definitely worth the effort. Compared to today’s limited AI, what people really want is artificial general intelligence, which will require new architectures that aren’t designed to solve one particular problem.
Until people start to explore, innovate, and play around with different designs, it’s not clear how we can further progress in the pursuit of general AI. A self-driving bike might not be much to look at, but its hybrid brain is a pretty neat place to start.
*The name, in Chinese, means “heavenly machine,” “unknowable mystery of nature,” or “confidentiality.” Go figure.
Image Credit: Alexander Ryabintsev / Shutterstock.com Continue reading
Posted in Human Robots
#434854 New Lifelike Biomaterial Self-Reproduces ...
Life demands flux.
Every living organism is constantly changing: cells divide and die, proteins build and disintegrate, DNA breaks and heals. Life demands metabolism—the simultaneous builder and destroyer of living materials—to continuously upgrade our bodies. That’s how we heal and grow, how we propagate and survive.
What if we could endow cold, static, lifeless robots with the gift of metabolism?
In a study published this month in Science Robotics, an international team developed a DNA-based method that gives raw biomaterials an artificial metabolism. Dubbed DASH—DNA-based assembly and synthesis of hierarchical materials—the method automatically generates “slime”-like nanobots that dynamically move and navigate their environments.
Like humans, the artificial lifelike material used external energy to constantly change the nanobots’ bodies in pre-programmed ways, recycling their DNA-based parts as both waste and raw material for further use. Some “grew” into the shape of molecular double-helixes; others “wrote” the DNA letters inside micro-chips.
The artificial life forms were also rather “competitive”—in quotes, because these molecular machines are not conscious. Yet when pitted against each other, two DASH bots automatically raced forward, crawling in typical slime-mold fashion at a scale easily seen under the microscope—and with some iterations, with the naked human eye.
“Fundamentally, we may be able to change how we create and use the materials with lifelike characteristics. Typically materials and objects we create in general are basically static… one day, we may be able to ‘grow’ objects like houses and maintain their forms and functions autonomously,” said study author Dr. Shogo Hamada to Singularity Hub.
“This is a great study that combines the versatility of DNA nanotechnology with the dynamics of living materials,” said Dr. Job Boekhoven at the Technical University of Munich, who was not involved in the work.
Dissipative Assembly
The study builds on previous ideas on how to make molecular Lego blocks that essentially assemble—and destroy—themselves.
Although the inspiration came from biological metabolism, scientists have long hoped to cut their reliance on nature. At its core, metabolism is just a bunch of well-coordinated chemical reactions, programmed by eons of evolution. So why build artificial lifelike materials still tethered by evolution when we can use chemistry to engineer completely new forms of artificial life?
Back in 2015, for example, a team led by Boekhoven described a way to mimic how our cells build their internal “structural beams,” aptly called the cytoskeleton. The key here, unlike many processes in nature, isn’t balance or equilibrium; rather, the team engineered an extremely unstable system that automatically builds—and sustains—assemblies from molecular building blocks when given an external source of chemical energy.
Sound familiar? The team basically built molecular devices that “die” without “food.” Thanks to the laws of thermodynamics (hey ya, Newton!), that energy eventually dissipates, and the shapes automatically begin to break down, completing an artificial “circle of life.”
The new study took the system one step further: rather than just mimicking synthesis, they completed the circle by coupling the building process with dissipative assembly.
Here, the “assembling units themselves are also autonomously created from scratch,” said Hamada.
DNA Nanobots
The process of building DNA nanobots starts on a microfluidic chip.
Decades of research have allowed researchers to optimize DNA assembly outside the body. With the help of catalysts, which help “bind” individual molecules together, the team found that they could easily alter the shape of the self-assembling DNA bots—which formed fiber-like shapes—by changing the structure of the microfluidic chambers.
Computer simulations played a role here too: through both digital simulations and observations under the microscope, the team was able to identify a few critical rules that helped them predict how their molecules self-assemble while navigating a maze of blocking “pillars” and channels carved onto the microchips.
This “enabled a general design strategy for the DASH patterns,” they said.
In particular, the whirling motion of the fluids as they coursed through—and bumped into—ridges in the chips seems to help the DNA molecules “entangle into networks,” the team explained.
These insights helped the team further develop the “destroying” part of metabolism. Similar to linking molecules into DNA chains, their destruction also relies on enzymes.
Once the team pumped both “generation” and “degeneration” enzymes into the microchips, along with raw building blocks, the process was completely autonomous. The simultaneous processes were so lifelike that the team used a metric commonly used in robotics, finite-state automation, to measure the behavior of their DNA nanobots from growth to eventual decay.
“The result is a synthetic structure with features associated with life. These behaviors include locomotion, self-regeneration, and spatiotemporal regulation,” said Boekhoven.
Molecular Slime Molds
Just witnessing lifelike molecules grow in place like the dance move running man wasn’t enough.
In their next experiments, the team took inspiration from slugs to program undulating movements into their DNA bots. Here, “movement” is actually a sort of illusion: the machines “moved” because their front ends kept regenerating, whereas their back ends degenerated. In essence, the molecular slime was built from linking multiple individual “DNA robot-like” units together: each unit receives a delayed “decay” signal from the head of the slime in a way that allowed the whole artificial “organism” to crawl forward, against the steam of fluid flow.
Here’s the fun part: the team eventually engineered two molecular slime bots and pitted them against each other, Mario Kart-style. In these experiments, the faster moving bot alters the state of its competitor to promote “decay.” This slows down the competitor, allowing the dominant DNA nanoslug to win in a race.
Of course, the end goal isn’t molecular podracing. Rather, the DNA-based bots could easily amplify a given DNA or RNA sequence, making them efficient nano-diagnosticians for viral and other infections.
The lifelike material can basically generate patterns that doctors can directly ‘see’ with their eyes, which makes DNA or RNA molecules from bacteria and viruses extremely easy to detect, the team said.
In the short run, “the detection device with this self-generating material could be applied to many places and help people on site, from farmers to clinics, by providing an easy and accurate way to detect pathogens,” explained Hamaga.
A Futuristic Iron Man Nanosuit?
I’m letting my nerd flag fly here. In Avengers: Infinity Wars, the scientist-engineer-philanthropist-playboy Tony Stark unveiled a nanosuit that grew to his contours when needed and automatically healed when damaged.
DASH may one day realize that vision. For now, the team isn’t focused on using the technology for regenerating armor—rather, the dynamic materials could create new protein assemblies or chemical pathways inside living organisms, for example. The team also envisions adding simple sensing and computing mechanisms into the material, which can then easily be thought of as a robot.
Unlike synthetic biology, the goal isn’t to create artificial life. Rather, the team hopes to give lifelike properties to otherwise static materials.
“We are introducing a brand-new, lifelike material concept powered by its very own artificial metabolism. We are not making something that’s alive, but we are creating materials that are much more lifelike than have ever been seen before,” said lead author Dr. Dan Luo.
“Ultimately, our material may allow the construction of self-reproducing machines… artificial metabolism is an important step toward the creation of ‘artificial’ biological systems with dynamic, lifelike capabilities,” added Hamada. “It could open a new frontier in robotics.”
Image Credit: A timelapse image of DASH, by Jeff Tyson at Cornell University. Continue reading
Posted in Human Robots
#434792 Extending Human Longevity With ...
Lizards can regrow entire limbs. Flatworms, starfish, and sea cucumbers regrow entire bodies. Sharks constantly replace lost teeth, often growing over 20,000 teeth throughout their lifetimes. How can we translate these near-superpowers to humans?
The answer: through the cutting-edge innovations of regenerative medicine.
While big data and artificial intelligence transform how we practice medicine and invent new treatments, regenerative medicine is about replenishing, replacing, and rejuvenating our physical bodies.
In Part 5 of this blog series on Longevity and Vitality, I detail three of the regenerative technologies working together to fully augment our vital human organs.
Replenish: Stem cells, the regenerative engine of the body
Replace: Organ regeneration and bioprinting
Rejuvenate: Young blood and parabiosis
Let’s dive in.
Replenish: Stem Cells – The Regenerative Engine of the Body
Stem cells are undifferentiated cells that can transform into specialized cells such as heart, neurons, liver, lung, skin and so on, and can also divide to produce more stem cells.
In a child or young adult, these stem cells are in large supply, acting as a built-in repair system. They are often summoned to the site of damage or inflammation to repair and restore normal function.
But as we age, our supply of stem cells begins to diminish as much as 100- to 10,000-fold in different tissues and organs. In addition, stem cells undergo genetic mutations, which reduce their quality and effectiveness at renovating and repairing your body.
Imagine your stem cells as a team of repairmen in your newly constructed mansion. When the mansion is new and the repairmen are young, they can fix everything perfectly. But as the repairmen age and reduce in number, your mansion eventually goes into disrepair and finally crumbles.
What if you could restore and rejuvenate your stem cell population?
One option to accomplish this restoration and rejuvenation is to extract and concentrate your own autologous adult stem cells from places like your adipose (or fat) tissue or bone marrow.
These stem cells, however, are fewer in number and have undergone mutations (depending on your age) from their original ‘software code.’ Many scientists and physicians now prefer an alternative source, obtaining stem cells from the placenta or umbilical cord, the leftovers of birth.
These stem cells, available in large supply and expressing the undamaged software of a newborn, can be injected into joints or administered intravenously to rejuvenate and revitalize.
Think of these stem cells as chemical factories generating vital growth factors that can help to reduce inflammation, fight autoimmune disease, increase muscle mass, repair joints, and even revitalize skin and grow hair.
Over the last decade, the number of publications per year on stem cell-related research has increased 40x, and the stem cell market is expected to increase to $297 billion by 2022.
Rising research and development initiatives to develop therapeutic options for chronic diseases and growing demand for regenerative treatment options are the most significant drivers of this budding industry.
Biologists led by Kohji Nishida at Osaka University in Japan have discovered a new way to nurture and grow the tissues that make up the human eyeball. The scientists are able to grow retinas, corneas, the eye’s lens, and more, using only a small sample of adult skin.
In a Stanford study, seven of 18 stroke victims who agreed to stem cell treatments showed remarkable motor function improvements. This treatment could work for other neurodegenerative conditions such as Alzheimer’s, Parkinson’s, and ALS.
Doctors from the USC Neurorestoration Center and Keck Medicine of USC injected stem cells into the damaged cervical spine of a recently paralyzed 21-year-old man. Three months later, he showed dramatic improvement in sensation and movement of both arms.
In 2019, doctors in the U.K. cured a patient with HIV for the second time ever thanks to the efficacy of stem cells. After giving the cancer patient (who also had HIV) an allogeneic haematopoietic (e.g. blood) stem cell treatment for his Hodgkin’s lymphoma, the patient went into long-term HIV remission—18 months and counting at the time of the study’s publication.
Replace: Organ Regeneration and 3D Printing
Every 10 minutes, someone is added to the US organ transplant waiting list, totaling over 113,000 people waiting for replacement organs as of January 2019.
Countless more people in need of ‘spare parts’ never make it onto the waiting list. And on average, 20 people die each day while waiting for a transplant.
As a result, 35 percent of all US deaths (~900,000 people) could be prevented or delayed with access to organ replacements.
The excessive demand for donated organs will only intensify as technologies like self-driving cars make the world safer, given that many organ donors result from auto and motorcycle accidents. Safer vehicles mean less accidents and donations.
Clearly, replacement and regenerative medicine represent a massive opportunity.
Organ Entrepreneurs
Enter United Therapeutics CEO, Dr. Martine Rothblatt. A one-time aerospace entrepreneur (she was the founder of Sirius Satellite Radio), Rothblatt changed careers in the 1990s after her daughter developed a rare lung disease.
Her moonshot today is to create an industry of replacement organs. With an initial focus on diseases of the lung, Rothblatt set out to create replacement lungs. To accomplish this goal, her company United Therapeutics has pursued a number of technologies in parallel.
3D Printing Lungs
In 2017, United teamed up with one of the world’s largest 3D printing companies, 3D Systems, to build a collagen bioprinter and is paying another company, 3Scan, to slice up lungs and create detailed maps of their interior.
This 3D Systems bioprinter now operates according to a method called stereolithography. A UV laser flickers through a shallow pool of collagen doped with photosensitive molecules. Wherever the laser lingers, the collagen cures and becomes solid.
Gradually, the object being printed is lowered and new layers are added. The printer can currently lay down collagen at a resolution of around 20 micrometers, but will need to achieve resolution of a micrometer in size to make the lung functional.
Once a collagen lung scaffold has been printed, the next step is to infuse it with human cells, a process called recellularization.
The goal here is to use stem cells that grow on scaffolding and differentiate, ultimately providing the proper functionality. Early evidence indicates this approach can work.
In 2018, Harvard University experimental surgeon Harald Ott reported that he pumped billions of human cells (from umbilical cords and diced lungs) into a pig lung stripped of its own cells. When Ott’s team reconnected it to a pig’s circulation, the resulting organ showed rudimentary function.
Humanizing Pig Lungs
Another of Rothblatt’s organ manufacturing strategies is called xenotransplantation, the idea of transplanting an animal’s organs into humans who need a replacement.
Given the fact that adult pig organs are similar in size and shape to those of humans, United Therapeutics has focused on genetically engineering pigs to allow humans to use their organs. “It’s actually not rocket science,” said Rothblatt in her 2015 TED talk. “It’s editing one gene after another.”
To accomplish this goal, United Therapeutics made a series of investments in companies such as Revivicor Inc. and Synthetic Genomics Inc., and signed large funding agreements with the University of Maryland, University of Alabama, and New York Presbyterian/Columbia University Medical Center to create xenotransplantation programs for new hearts, kidneys, and lungs, respectively. Rothblatt hopes to see human translation in three to four years.
In preparation for that day, United Therapeutics owns a 132-acre property in Research Triangle Park and built a 275,000-square-foot medical laboratory that will ultimately have the capability to annually produce up to 1,000 sets of healthy pig lungs—known as xenolungs—from genetically engineered pigs.
Lung Ex Vivo Perfusion Systems
Beyond 3D printing and genetically engineering pig lungs, Rothblatt has already begun implementing a third near-term approach to improve the supply of lungs across the US.
Only about 30 percent of potential donor lungs meet transplant criteria in the first place; of those, only about 85 percent of those are usable once they arrive at the surgery center. As a result, nearly 75 percent of possible lungs never make it to the recipient in need.
What if these lungs could be rejuvenated? This concept informs Dr. Rothblatt’s next approach.
In 2016, United Therapeutics invested $41.8 million in TransMedics Inc., an Andover, Massachusetts company that develops ex vivo perfusion systems for donor lungs, hearts, and kidneys.
The XVIVO Perfusion System takes marginal-quality lungs that initially failed to meet transplantation standard-of-care criteria and perfuses and ventilates them at normothermic conditions, providing an opportunity for surgeons to reassess transplant suitability.
Rejuvenate Young Blood and Parabiosis
In HBO’s parody of the Bay Area tech community, Silicon Valley, one of the episodes (Season 4, Episode 5) is named “The Blood Boy.”
In this installment, tech billionaire Gavin Belson (Matt Ross) is meeting with Richard Hendricks (Thomas Middleditch) and his team, speaking about the future of the decentralized internet. A young, muscled twenty-something disrupts the meeting when he rolls in a transfusion stand and silently hooks an intravenous connection between himself and Belson.
Belson then introduces the newcomer as his “transfusion associate” and begins to explain the science of parabiosis: “Regular transfusions of the blood of a younger physically fit donor can significantly retard the aging process.”
While the sitcom is fiction, that science has merit, and the scenario portrayed in the episode is already happening today.
On the first point, research at Stanford and Harvard has demonstrated that older animals, when transfused with the blood of young animals, experience regeneration across many tissues and organs.
The opposite is also true: young animals, when transfused with the blood of older animals, experience accelerated aging. But capitalizing on this virtual fountain of youth has been tricky.
Ambrosia
One company, a San Francisco-based startup called Ambrosia, recently commenced one of the trials on parabiosis. Their protocol is simple: Healthy participants aged 35 and older get a transfusion of blood plasma from donors under 25, and researchers monitor their blood over the next two years for molecular indicators of health and aging.
Ambrosia’s founder Jesse Karmazin became interested in launching a company around parabiosis after seeing impressive data from animals and studies conducted abroad in humans: In one trial after another, subjects experience a reversal of aging symptoms across every major organ system. “The effects seem to be almost permanent,” he said. “It’s almost like there’s a resetting of gene expression.”
Infusing your own cord blood stem cells as you age may have tremendous longevity benefits. Following an FDA press release in February 2019, Ambrosia halted its consumer-facing treatment after several months of operation.
Understandably, the FDA raised concerns about the practice of parabiosis because to date, there is a marked lack of clinical data to support the treatment’s effectiveness.
Elevian
On the other end of the reputability spectrum is a startup called Elevian, spun out of Harvard University. Elevian is approaching longevity with a careful, scientifically validated strategy. (Full Disclosure: I am both an advisor to and investor in Elevian.)
CEO Mark Allen, MD, is joined by a dozen MDs and Ph.Ds out of Harvard. Elevian’s scientific founders started the company after identifying specific circulating factors that may be responsible for the “young blood” effect.
One example: A naturally occurring molecule known as “growth differentiation factor 11,” or GDF11, when injected into aged mice, reproduces many of the regenerative effects of young blood, regenerating heart, brain, muscles, lungs, and kidneys.
More specifically, GDF11 supplementation reduces age-related cardiac hypertrophy, accelerates skeletal muscle repair, improves exercise capacity, improves brain function and cerebral blood flow, and improves metabolism.
Elevian is developing a number of therapeutics that regulate GDF11 and other circulating factors. The goal is to restore our body’s natural regenerative capacity, which Elevian believes can address some of the root causes of age-associated disease with the promise of reversing or preventing many aging-related diseases and extending the healthy lifespan.
Conclusion
In 1992, futurist Leland Kaiser coined the term “regenerative medicine”:
“A new branch of medicine will develop that attempts to change the course of chronic disease and in many instances will regenerate tired and failing organ systems.”
Since then, the powerful regenerative medicine industry has grown exponentially, and this rapid growth is anticipated to continue.
A dramatic extension of the human healthspan is just over the horizon. Soon, we’ll all have the regenerative superpowers previously relegated to a handful of animals and comic books.
What new opportunities open up when anybody, anywhere, and at anytime can regenerate, replenish, and replace entire organs and metabolic systems on command?
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Posted in Human Robots
#434580 How Genome Sequencing and Senolytics Can ...
The causes of aging are extremely complex and unclear. With the dramatic demonetization of genome reading and editing over the past decade, and Big Pharma, startups, and the FDA starting to face aging as a disease, we are starting to find practical ways to extend our healthspan.
Here, in Part 2 of a series of blogs on longevity and vitality, I explore how genome sequencing and editing, along with new classes of anti-aging drugs, are augmenting our biology to further extend our healthy lives.
In this blog I’ll cover two classes of emerging technologies:
Genome Sequencing and Editing;
Senolytics, Nutraceuticals & Pharmaceuticals.
Let’s dive in.
Genome Sequencing & Editing
Your genome is the software that runs your body.
A sequence of 3.2 billion letters makes you “you.” These base pairs of A’s, T’s, C’s, and G’s determine your hair color, your height, your personality, your propensity to disease, your lifespan, and so on.
Until recently, it’s been very difficult to rapidly and cheaply “read” these letters—and even more difficult to understand what they mean.
Since 2001, the cost to sequence a whole human genome has plummeted exponentially, outpacing Moore’s Law threefold. From an initial cost of $3.7 billion, it dropped to $10 million in 2006, and to $5,000 in 2012.
Today, the cost of genome sequencing has dropped below $500, and according to Illumina, the world’s leading sequencing company, the process will soon cost about $100 and take about an hour to complete.
This represents one of the most powerful and transformative technology revolutions in healthcare.
When we understand your genome, we’ll be able to understand how to optimize “you.”
We’ll know the perfect foods, the perfect drugs, the perfect exercise regimen, and the perfect supplements, just for you.
We’ll understand what microbiome types, or gut flora, are ideal for you (more on this in a later blog).
We’ll accurately predict how specific sedatives and medicines will impact you.
We’ll learn which diseases and illnesses you’re most likely to develop and, more importantly, how to best prevent them from developing in the first place (rather than trying to cure them after the fact).
CRISPR Gene Editing
In addition to reading the human genome, scientists can now edit a genome using a naturally-occurring biological system discovered in 1987 called CRISPR/Cas9.
Short for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9, the editing system was adapted from a naturally-occurring defense system found in bacteria.
Here’s how it works:
The bacteria capture snippets of DNA from invading viruses (or bacteriophage) and use them to create DNA segments known as CRISPR arrays.
The CRISPR arrays allow the bacteria to “remember” the viruses (or closely related ones), and defend against future invasions.
If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses’ DNA. The bacteria then use Cas9 to cut the DNA apart, which disables the virus.
Most importantly, CRISPR is cheap, quick, easy to use, and more accurate than all previous gene editing methods. As a result, CRISPR/Cas9 has swept through labs around the world as the way to edit a genome.
A short search in the literature will show an exponential rise in the number of CRISPR-related publications and patents.
2018: Filled With CRISPR Breakthroughs
Early results are impressive. Researchers from the University of Chicago recently used CRISPR to genetically engineer cocaine resistance into mice.
Researchers at the University of Texas Southwestern Medical Center used CRISPR to reverse the gene defect causing Duchenne muscular dystrophy (DMD) in dogs (DMD is the most common fatal genetic disease in children).
With great power comes great responsibility, and moral and ethical dilemmas.
In 2015, Chinese scientists sparked global controversy when they first edited human embryo cells in the lab with the goal of modifying genes that would make the child resistant to smallpox, HIV, and cholera.
Three years later, in November 2018, researcher He Jiankui informed the world that the first set of CRISPR-engineered female twins had been delivered.
To accomplish his goal, Jiankui deleted a region of a receptor on the surface of white blood cells known as CCR5, introducing a rare, natural genetic variation that makes it more difficult for HIV to infect its favorite target, white blood cells.
Setting aside the significant ethical conversations, CRISPR will soon provide us the tools to eliminate diseases, create hardier offspring, produce new environmentally resistant crops, and even wipe out pathogens.
Senolytics, Nutraceuticals & Pharmaceuticals
Over the arc of your life, the cells in your body divide until they reach what is known as the Hayflick limit, or the number of times a normal human cell population will divide before cell division stops, which is typically about 50 divisions.
What normally follows next is programmed cell death or destruction by the immune system. A very small fraction of cells, however, become senescent cells and evade this fate to linger indefinitely.
These lingering cells secrete a potent mix of molecules that triggers chronic inflammation, damages the surrounding tissue structures, and changes the behavior of nearby cells for the worse.
Senescent cells appear to be one of the root causes of aging, causing everything from fibrosis and blood vessel calcification, to localized inflammatory conditions such as osteoarthritis, to diminished lung function.
Fortunately, both the scientific and entrepreneurial communities have begun to work on senolytic therapies, moving the technology for selectively destroying senescent cells out of the laboratory and into a half-dozen startup companies.
Prominent companies in the field include the following:
Unity Biotechnology is developing senolytic medicines to selectively eliminate senescent cells with an initial focus on delivering localized therapy in osteoarthritis, ophthalmology and pulmonary disease.
Oisin Biotechnologiesis pioneering a programmable gene therapy that can destroy cells based on their internal biochemistry.
SIWA Therapeuticsis working on an immunotherapy approach to the problem of senescent cells.
In recent years, researchers have identified or designed a handful of senolytic compounds that can curb aging by regulating senescent cells. Two of these drugs that have gained mainstay research traction are rapamycin and metformin.
Rapamycin
Originally extracted from bacteria found on Easter Island, Rapamycin acts on the m-TOR (mechanistic target of rapamycin) pathway to selectively block a key protein that facilitates cell division.
Currently, rapamycin derivatives are widely used as immunosuppression in organ and bone marrow transplants. Research now suggests that use results in prolonged lifespan and enhanced cognitive and immune function.
PureTech Health subsidiary resTORbio (which started 2018 by going public) is working on a rapamycin-based drug intended to enhance immunity and reduce infection. Their clinical-stage RTB101 drug works by inhibiting part of the mTOR pathway.
Results of the drug’s recent clinical trial include:
Decreased incidence of infection
Improved influenza vaccination response
A 30.6 percent decrease in respiratory tract infections
Impressive, to say the least.
Metformin
Metformin is a widely-used generic drug for mitigating liver sugar production in Type 2 diabetes patients.
Researchers have found that Metformin also reduces oxidative stress and inflammation, which otherwise increase as we age.
There is strong evidence that Metformin can augment cellular regeneration and dramatically mitigate cellular senescence by reducing both oxidative stress and inflammation.
Over 100 studies registered on ClinicalTrials.gov are currently following up on strong evidence of Metformin’s protective effect against cancer.
Nutraceuticals and NAD+
Beyond cellular senescence, certain critical nutrients and proteins tend to decline as a function of age. Nutraceuticals combat aging by supplementing and replenishing these declining nutrient levels.
NAD+ exists in every cell, participating in every process from DNA repair to creating the energy vital for cellular processes. It’s been shown that NAD+ levels decline as we age.
The Elysium Health Basis supplement aims to elevate NAD+ levels in the body to extend one’s lifespan. Elysium’s clinical study reports that Basis increases NAD+ levels consistently by a sustained 40 percent.
Conclusion
These are just a taste of the tremendous momentum that longevity and aging technology has right now. As artificial intelligence and quantum computing transform how we decode our DNA and how we discover drugs, genetics and pharmaceuticals will become truly personalized.
The next blog in this series will demonstrate how artificial intelligence is converging with genetics and pharmaceuticals to transform how we approach longevity, aging, and vitality.
We are edging closer to a dramatically extended healthspan—where 100 is the new 60. What will you create, where will you explore, and how will you spend your time if you are able to add an additional 40 healthy years to your life?
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