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The causes of aging are extremely complex and unclear. But with longevity clinical trials increasing, more answers—and questions—are emerging than ever before.
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 turn those answers into practical ways to extend our healthspan.
In this article, I’ll explore how genome sequencing and editing, along with new classes of anti-aging drugs, are augmenting our biology to further extend our healthy lives.
Genome Sequencing and 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 for 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 $1,500 in 2015.
Today, the cost of genome sequencing has dropped below $600, 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 article).
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 have used CRISPR to genetically engineer cocaine resistance into mice, reverse the gene defect causing Duchenne muscular dystrophy (DMD) in dogs, and reduce genetic deafness in mice.
Already this year, CRISPR-edited immune cells have been shown to successfully kill cancer cells in human patients. Researchers have discovered ways to activate CRISPR with light and use the gene-editing technology to better understand Alzheimer’s disease progression.
With great power comes great responsibility, and the opportunity for 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. Because Jiankui forged ethical review documents and misled doctors in the process, he was sentenced to three years in prison and fined $429,000 last December.
Coupled with significant ethical conversations necessary for progress, 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, and 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 Biotechnologies is pioneering a programmable gene therapy that can destroy cells based on their internal biochemistry.
SIWA Therapeutics is 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.
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 for 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 went public in 2018) 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, and a 30.6 percent decrease in respiratory tract infection.
Impressive, to say the least.
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.
(3) 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 first clinical study reports that Basis increases NAD+ levels consistently by a sustained 40 percent.
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 article 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 toward 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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(Both A360 and Abundance-Digital are part of Singularity University—your participation opens you to a global community.)
This article originally appeared on diamandis.com. Read the original article here.
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The human brain operates on roughly 20 watts of power (a third of a 60-watt light bulb) in a space the size of, well, a human head. The biggest machine learning algorithms use closer to a nuclear power plant’s worth of electricity and racks of chips to learn.
That’s not to slander machine learning, but nature may have a tip or two to improve the situation. Luckily, there’s a branch of computer chip design heeding that call. By mimicking the brain, super-efficient neuromorphic chips aim to take AI off the cloud and put it in your pocket.
The latest such chip is smaller than a piece of confetti and has tens of thousands of artificial synapses made out of memristors—chip components that can mimic their natural counterparts in the brain.
In a recent paper in Nature Nanotechnology, a team of MIT scientists say their tiny new neuromorphic chip was used to store, retrieve, and manipulate images of Captain America’s Shield and MIT’s Killian Court. Whereas images stored with existing methods tended to lose fidelity over time, the new chip’s images remained crystal clear.
“So far, artificial synapse networks exist as software. We’re trying to build real neural network hardware for portable artificial intelligence systems,” Jeehwan Kim, associate professor of mechanical engineering at MIT said in a press release. “Imagine connecting a neuromorphic device to a camera on your car, and having it recognize lights and objects and make a decision immediately, without having to connect to the internet. We hope to use energy-efficient memristors to do those tasks on-site, in real-time.”
A Brain in Your Pocket
Whereas the computers in our phones and laptops use separate digital components for processing and memory—and therefore need to shuttle information between the two—the MIT chip uses analog components called memristors that process and store information in the same place. This is similar to the way the brain works and makes memristors far more efficient. To date, however, they’ve struggled with reliability and scalability.
To overcome these challenges, the MIT team designed a new kind of silicon-based, alloyed memristor. Ions flowing in memristors made from unalloyed materials tend to scatter as the components get smaller, meaning the signal loses fidelity and the resulting computations are less reliable. The team found an alloy of silver and copper helped stabilize the flow of silver ions between electrodes, allowing them to scale the number of memristors on the chip without sacrificing functionality.
While MIT’s new chip is promising, there’s likely a ways to go before memristor-based neuromorphic chips go mainstream. Between now and then, engineers like Kim have their work cut out for them to further scale and demonstrate their designs. But if successful, they could make for smarter smartphones and other even smaller devices.
“We would like to develop this technology further to have larger-scale arrays to do image recognition tasks,” Kim said. “And some day, you might be able to carry around artificial brains to do these kinds of tasks, without connecting to supercomputers, the internet, or the cloud.”
Special Chips for AI
The MIT work is part of a larger trend in computing and machine learning. As progress in classical chips has flagged in recent years, there’s been an increasing focus on more efficient software and specialized chips to continue pushing the pace.
Neuromorphic chips, for example, aren’t new. IBM and Intel are developing their own designs. So far, their chips have been based on groups of standard computing components, such as transistors (as opposed to memristors), arranged to imitate neurons in the brain. These chips are, however, still in the research phase.
Graphics processing units (GPUs)—chips originally developed for graphics-heavy work like video games—are the best practical example of specialized hardware for AI and were heavily used in this generation of machine learning early on. In the years since, Google, NVIDIA, and others have developed even more specialized chips that cater more specifically to machine learning.
The gains from such specialized chips are already being felt.
In a recent cost analysis of machine learning, research and investment firm ARK Invest said cost declines have far outpaced Moore’s Law. In a particular example, they found the cost to train an image recognition algorithm (ResNet-50) went from around $1,000 in 2017 to roughly $10 in 2019. The fall in cost to actually run such an algorithm was even more dramatic. It took $10,000 to classify a billion images in 2017 and just $0.03 in 2019.
Some of these declines can be traced to better software, but according to ARK, specialized chips have improved performance by nearly 16 times in the last three years.
As neuromorphic chips—and other tailored designs—advance further in the years to come, these trends in cost and performance may continue. Eventually, if all goes to plan, we might all carry a pocket brain that can do the work of today’s best AI.
Image credit: Peng Lin Continue reading
Creativity is a trait that makes humans unique from other species. We alone have the ability to make music and art that speak to our experiences or illuminate truths about our world. But suddenly, humans’ artistic abilities have some competition—and from a decidedly non-human source.
Over the last couple years there have been some remarkable examples of art produced by deep learning algorithms. They have challenged the notion of an elusive definition of creativity and put into perspective how professionals can use artificial intelligence to enhance their abilities and produce beyond the known boundaries.
But when creativity is the result of code written by a programmer, using a format given by a software engineer, featuring private and public datasets, how do we assign ownership of AI-generated content, and particularly that of artwork? McKinsey estimates AI will annually generate value of $3.5 to $5.8 trillion across various sectors.
In 2018, a portrait that was christened Edmond de Belamy was made in a French art collective called Obvious. It used a database with 15,000 portraits from the 1300s to the 1900s to train a deep learning algorithm to produce a unique portrait. The painting sold for $432,500 in a New York auction. Similarly, a program called Aiva, trained on thousands of classical compositions, has released albums whose pieces are being used by ad agencies and movies.
The datasets used by these algorithms were different, but behind both there was a programmer who changed the brush strokes or musical notes into lines of code and a data scientist or engineer who fitted and “curated” the datasets to use for the model. There could also have been user-based input, and the output may be biased towards certain styles or unintentionally infringe on similar pieces of art. This shows that there are many collaborators with distinct roles in producing AI-generated content, and it’s important to discuss how they can protect their proprietary interests.
A perspective article published in Nature Machine Intelligence by Jason K. Eshraghian in March looks into how AI artists and the collaborators involved should assess their ownership, laying out some guiding principles that are “only applicable for as long as AI does not have legal parenthood, the way humans and corporations are accorded.”
Before looking at how collaborators can protect their interests, it’s useful to understand the basic requirements of copyright law. The artwork in question must be an “original work of authorship fixed in a tangible medium.” Given this principle, the author asked whether it’s possible for AI to exercise creativity, skill, or any other indicator of originality. The answer is still straightforward—no—or at least not yet. Currently, AI’s range of creativity doesn’t exceed the standard used by the US Copyright Office, which states that copyright law protects the “fruits of intellectual labor founded in the creative powers of the mind.”
Due to the current limitations of narrow AI, it must have some form of initial input that helps develop its ability to create. At the moment AI is a tool that can be used to produce creative work in the same way that a video camera is a tool used to film creative content. Video producers don’t need to comprehend the inner workings of their cameras; as long as their content shows creativity and originality, they have a proprietary claim over their creations.
The same concept applies to programmers developing a neural network. As long as the dataset they use as input yields an original and creative result, it will be protected by copyright law; they don’t need to understand the high-level mathematics, which in this case are often black box algorithms whose output it’s impossible to analyze.
Will robots and algorithms eventually be treated as creative sources able to own copyrights? The author pointed to the recent patent case of Warner-Lambert Co Ltd versus Generics where Lord Briggs, Justice of the Supreme Court of the UK, determined that “the court is well versed in identifying the governing mind of a corporation and, when the need arises, will no doubt be able to do the same for robots.”
In the meantime, Dr. Eshraghian suggests four guiding principles to allow artists who collaborate with AI to protect themselves.
First, programmers need to document their process through online code repositories like GitHub or BitBucket.
Second, data engineers should also document and catalog their datasets and the process they used to curate their models, indicating selectivity in their criteria as much as possible to demonstrate their involvement and creativity.
Third, in cases where user data is utilized, the engineer should “catalog all runs of the program” to distinguish the data selection process. This could be interpreted as a way of determining whether user-based input has a right to claim the copyright too.
Finally, the output should avoid infringing on others’ content through methods like reverse image searches and version control, as mentioned above.
AI-generated artwork is still a very new concept, and the ambiguous copyright laws around it give a lot of flexibility to AI artists and programmers worldwide. The guiding principles Eshraghian lays out will hopefully shed some light on the legislation we’ll eventually need for this kind of art, and start an important conversation between all the stakeholders involved.
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Scientists have linked up two silicon-based artificial neurons with a biological one across multiple countries into a fully-functional network. Using standard internet protocols, they established a chain of communication whereby an artificial neuron controls a living, biological one, and passes on the info to another artificial one.
We’ve talked plenty about brain-computer interfaces and novel computer chips that resemble the brain. We’ve covered how those “neuromorphic” chips could link up into tremendously powerful computing entities, using engineered communication nodes called artificial synapses.
As Moore’s law is dying, we even said that neuromorphic computing is one path towards the future of extremely powerful, low energy consumption artificial neural network-based computing—in hardware—that could in theory better link up with the brain. Because the chips “speak” the brain’s language, in theory they could become neuroprosthesis hubs far more advanced and “natural” than anything currently possible.
This month, an international team put all of those ingredients together, turning theory into reality.
The three labs, scattered across Padova, Italy, Zurich, Switzerland, and Southampton, England, collaborated to create a fully self-controlled, hybrid artificial-biological neural network that communicated using biological principles, but over the internet.
The three-neuron network, linked through artificial synapses that emulate the real thing, was able to reproduce a classic neuroscience experiment that’s considered the basis of learning and memory in the brain. In other words, artificial neuron and synapse “chips” have progressed to the point where they can actually use a biological neuron intermediary to form a circuit that, at least partially, behaves like the real thing.
That’s not to say cyborg brains are coming soon. The simulation only recreated a small network that supports excitatory transmission in the hippocampus—a critical region that supports memory—and most brain functions require enormous cross-talk between numerous neurons and circuits. Nevertheless, the study is a jaw-dropping demonstration of how far we’ve come in recreating biological neurons and synapses in artificial hardware.
And perhaps one day, the currently “experimental” neuromorphic hardware will be integrated into broken biological neural circuits as bridges to restore movement, memory, personality, and even a sense of self.
The Artificial Brain Boom
One important thing: this study relies heavily on a decade of research into neuromorphic computing, or the implementation of brain functions inside computer chips.
The best-known example is perhaps IBM’s TrueNorth, which leveraged the brain’s computational principles to build a completely different computer than what we have today. Today’s computers run on a von Neumann architecture, in which memory and processing modules are physically separate. In contrast, the brain’s computing and memory are simultaneously achieved at synapses, small “hubs” on individual neurons that talk to adjacent ones.
Because memory and processing occur on the same site, biological neurons don’t have to shuttle data back and forth between processing and storage compartments, massively reducing processing time and energy use. What’s more, a neuron’s history will also influence how it behaves in the future, increasing flexibility and adaptability compared to computers. With the rise of deep learning, which loosely mimics neural processing as the prima donna of AI, the need to reduce power while boosting speed and flexible learning is becoming ever more tantamount in the AI community.
Neuromorphic computing was partially born out of this need. Most chips utilize special ingredients that change their resistance (or other physical characteristics) to mimic how a neuron might adapt to stimulation. Some chips emulate a whole neuron, that is, how it responds to a history of stimulation—does it get easier or harder to fire? Others imitate synapses themselves, that is, how easily they will pass on the information to another neuron.
Although single neuromorphic chips have proven to be far more efficient and powerful than current computer chips running machine learning algorithms in toy problems, so far few people have tried putting the artificial components together with biological ones in the ultimate test.
That’s what this study did.
A Hybrid Network
Still with me? Let’s talk network.
It’s gonna sound complicated, but remember: learning is the formation of neural networks, and neurons that fire together wire together. To rephrase: when learning, neurons will spontaneously organize into networks so that future instances will re-trigger the entire network. To “wire” together, downstream neurons will become more responsive to their upstream neural partners, so that even a whisper will cause them to activate. In contrast, some types of stimulation will cause the downstream neuron to “chill out” so that only an upstream “shout” will trigger downstream activation.
Both these properties—easier or harder to activate downstream neurons—are essentially how the brain forms connections. The “amping up,” in neuroscience jargon, is long-term potentiation (LTP), whereas the down-tuning is LTD (long-term depression). These two phenomena were first discovered in the rodent hippocampus more than half a century ago, and ever since have been considered as the biological basis of how the brain learns and remembers, and implicated in neurological problems such as addition (seriously, you can’t pass Neuro 101 without learning about LTP and LTD!).
So it’s perhaps especially salient that one of the first artificial-brain hybrid networks recapitulated this classic result.
To visualize: the three-neuron network began in Switzerland, with an artificial neuron with the badass name of “silicon spiking neuron.” That neuron is linked to an artificial synapse, a “memristor” located in the UK, which is then linked to a biological rat neuron cultured in Italy. The rat neuron has a “smart” microelectrode, controlled by the artificial synapse, to stimulate it. This is the artificial-to-biological pathway.
Meanwhile, the rat neuron in Italy also has electrodes that listen in on its electrical signaling. This signaling is passed back to another artificial synapse in the UK, which is then used to control a second artificial neuron back in Switzerland. This is the biological-to-artificial pathway back. As a testimony in how far we’ve come in digitizing neural signaling, all of the biological neural responses are digitized and sent over the internet to control its far-out artificial partner.
Here’s the crux: to demonstrate a functional neural network, just having the biological neuron passively “pass on” electrical stimulation isn’t enough. It has to show the capacity to learn, that is, to be able to mimic the amping up and down-tuning that are LTP and LTD, respectively.
You’ve probably guessed the results: certain stimulation patterns to the first artificial neuron in Switzerland changed how the artificial synapse in the UK operated. This, in turn, changed the stimulation to the biological neuron, so that it either amped up or toned down depending on the input.
Similarly, the response of the biological neuron altered the second artificial synapse, which then controlled the output of the second artificial neuron. Altogether, the biological and artificial components seamlessly linked up, over thousands of miles, into a functional neural circuit.
So…I’m still picking my jaw up off the floor.
It’s utterly insane seeing a classic neuroscience learning experiment repeated with an integrated network with artificial components. That said, a three-neuron network is far from the thousands of synapses (if not more) needed to truly re-establish a broken neural circuit in the hippocampus, which DARPA has been aiming to do. And LTP/LTD has come under fire recently as the de facto brain mechanism for learning, though so far they remain cemented as neuroscience dogma.
However, this is one of the few studies where you see fields coming together. As Richard Feynman famously said, “What I cannot recreate, I cannot understand.” Even though neuromorphic chips were built on a high-level rather than molecular-level understanding of how neurons work, the study shows that artificial versions can still synapse with their biological counterparts. We’re not just on the right path towards understanding the brain, we’re recreating it, in hardware—if just a little.
While the study doesn’t have immediate use cases, practically it does boost both the neuromorphic computing and neuroprosthetic fields.
“We are very excited with this new development,” said study author Dr. Themis Prodromakis at the University of Southampton. “On one side it sets the basis for a novel scenario that was never encountered during natural evolution, where biological and artificial neurons are linked together and communicate across global networks; laying the foundations for the Internet of Neuro-electronics. On the other hand, it brings new prospects to neuroprosthetic technologies, paving the way towards research into replacing dysfunctional parts of the brain with AI chips.”
Image Credit: Gerd Altmann from Pixabay Continue reading