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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.
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 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.
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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It’s common to hear phrases like ‘machine learning’ and ‘artificial intelligence’ and believe that somehow, someone has managed to replicate a human mind inside a computer. This, of course, is untrue—but part of the reason this idea is so pervasive is because the metaphor of human learning and intelligence has been quite useful in explaining machine learning and artificial intelligence.
Indeed, some AI researchers maintain a close link with the neuroscience community, and inspiration runs in both directions. But the metaphor can be a hindrance to people trying to explain machine learning to those less familiar with it. One of the biggest risks of conflating human and machine intelligence is that we start to hand over too much agency to machines. For those of us working with software, it’s essential that we remember the agency is human—it’s humans who build these systems, after all.
It’s worth unpacking the key differences between machine and human intelligence. While there are certainly similarities, it’s by looking at what makes them different that we can better grasp how artificial intelligence works, and how we can build and use it effectively.
Central to the metaphor that links human and machine learning is the concept of a neural network. The biggest difference between a human brain and an artificial neural net is the sheer scale of the brain’s neural network. What’s crucial is that it’s not simply the number of neurons in the brain (which reach into the billions), but more precisely, the mind-boggling number of connections between them.
But the issue runs deeper than questions of scale. The human brain is qualitatively different from an artificial neural network for two other important reasons: the connections that power it are analogue, not digital, and the neurons themselves aren’t uniform (as they are in an artificial neural network).
This is why the brain is such a complex thing. Even the most complex artificial neural network, while often difficult to interpret and unpack, has an underlying architecture and principles guiding it (this is what we’re trying to do, so let’s construct the network like this…).
Intricate as they may be, neural networks in AIs are engineered with a specific outcome in mind. The human mind, however, doesn’t have the same degree of intentionality in its engineering. Yes, it should help us do all the things we need to do to stay alive, but it also allows us to think critically and creatively in a way that doesn’t need to be programmed.
The Beautiful Simplicity of AI
The fact that artificial intelligence systems are so much simpler than the human brain is, ironically, what enables AIs to deal with far greater computational complexity than we can.
Artificial neural networks can hold much more information and data than the human brain, largely due to the type of data that is stored and processed in a neural network. It is discrete and specific, like an entry on an excel spreadsheet.
In the human brain, data doesn’t have this same discrete quality. So while an artificial neural network can process very specific data at an incredible scale, it isn’t able to process information in the rich and multidimensional manner a human brain can. This is the key difference between an engineered system and the human mind.
Despite years of research, the human mind still remains somewhat opaque. This is because the analog synaptic connections between neurons are almost impenetrable to the digital connections within an artificial neural network.
Speed and Scale
Consider what this means in practice. The relative simplicity of an AI allows it to do a very complex task very well, and very quickly. A human brain simply can’t process data at scale and speed in the way AIs need to if they’re, say, translating speech to text, or processing a huge set of oncology reports.
Essential to the way AI works in both these contexts is that it breaks data and information down into tiny constituent parts. For example, it could break sounds down into phonetic text, which could then be translated into full sentences, or break images into pieces to understand the rules of how a huge set of them is composed.
Humans often do a similar thing, and this is the point at which machine learning is most like human learning; like algorithms, humans break data or information into smaller chunks in order to process it.
But there’s a reason for this similarity. This breakdown process is engineered into every neural network by a human engineer. What’s more, the way this process is designed will be down to the problem at hand. How an artificial intelligence system breaks down a data set is its own way of ‘understanding’ it.
Even while running a highly complex algorithm unsupervised, the parameters of how an AI learns—how it breaks data down in order to process it—are always set from the start.
Human Intelligence: Defining Problems
Human intelligence doesn’t have this set of limitations, which is what makes us so much more effective at problem-solving. It’s the human ability to ‘create’ problems that makes us so good at solving them. There’s an element of contextual understanding and decision-making in the way humans approach problems.
AIs might be able to unpack problems or find new ways into them, but they can’t define the problem they’re trying to solve.
Algorithmic insensitivity has come into focus in recent years, with an increasing number of scandals around bias in AI systems. Of course, this is caused by the biases of those making the algorithms, but underlines the point that algorithmic biases can only be identified by human intelligence.
Human and Artificial Intelligence Should Complement Each Other
We must remember that artificial intelligence and machine learning aren’t simply things that ‘exist’ that we can no longer control. They are built, engineered, and designed by us. This mindset puts us in control of the future, and makes algorithms even more elegant and remarkable.
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Disruptive business models are often powered by alternative financing. In Part 1 of this series, I discussed how mobile is redefining money and banking and shared some of the dramatic transformations in the global remittance infrastructure.
In this article, we’ll discuss:
AI financial advisors and robo traders
Let’s dive right back in…
Decentralized Lending = Democratized Access to Finances
Peer-to-peer (P2P) lending is an age-old practice, traditionally with high risk and extreme locality. Now, the P2P funding model is being digitized and delocalized, bringing lending online and across borders.
Zopa, the first official crowdlending platform, arrived in the United Kingdom in 2004. Since then, the consumer crowdlending platform has facilitated lending of over 3 billion euros ($3.5 billion USD) of loans.
Person-to-business crowdlending took off, again in the U.K., in 2005 with Funding Circle, now with over 5 billion euros (~5.8 billion USD) of capital loaned to small businesses around the world.
Crowdlending next took off in the US in 2006, with platforms like Prosper and Lending Club. The US crowdlending industry has boomed to $21 billion in loans, across 515,000 loans.
Let’s take a step back… to a time before banks, when lending took place between trusted neighbors in small villages across the globe. Lending started as peer-to-peer transactions.
As villages turned into towns, towns turned into cities, and cities turned into sprawling metropolises, neighborly trust and the ability to communicate across urban landscapes broke down. That’s where banks and other financial institutions came into play—to add trust back into the lending equation.
With crowdlending, we are evidently returning to this pre-centralized-banking model of loans, and moving away from cumbersome intermediaries (e.g. high fees, regulations, and extra complexity).
Fueled by the permeation of the internet, P2P lending took on a new form as ‘crowdlending’ in the early 2000s. Now, as blockchain and artificial intelligence arrive on the digital scene, P2P lending platforms are being overhauled with transparency, accountability, reliability, and immutability.
Artificial Intelligence Micro Lending & Credit Scores
We are beginning to augment our quantitative decision-making with neural networks processing borrowers’ financial data to determine their financial ‘fate’ (or, as some call it, your credit score). Companies like Smart Finance Group (backed by Kai Fu Lee and Sinovation Ventures) are using artificial intelligence to minimize default rates for tens of millions of microloans.
Smart Finance is fueled by users’ personal data, particularly smartphone data and usage behavior. Users are required to give Smart Finance access to their smartphone data, so that Smart Finance’s artificial intelligence engine can generate a credit score from the personal information.
The benefits of this AI-powered lending platform do not stop at increased loan payback rates; there’s a massive speed increase as well. Smart Finance loans are frequently approved in under eight seconds. As we’ve seen with other artificial intelligence disruptions, data is the new gold.
Digitizing access to P2P loans paves the way for billions of people currently without access to banking to leapfrog the centralized banking system, just as Africa bypassed landline phones and went straight to mobile. Leapfrogging centralized banking and the credit system is exactly what Smart Finance has done for hundreds of millions of people in China.
As artificial intelligence accesses even the most mundane mobile browsing data to assign credit scores, blockchain technologies, particularly immutable ledgers and smart contracts, are massive disruptors to the archaic banking system, building additional trust and transparency on top of current P2P lending models.
Immutable ledgers provide the necessary transparency for accurate credit and loan defaulting history. Smart contracts executed on these immutable ledgers bring the critical ability to digitally replace cumbersome, expensive third parties (like banks), allowing individual borrowers or businesses to directly connect with willing lenders.
Two of the leading blockchain platforms for P2P lending are ETHLend and SALT Lending.
ETHLend is an Ethereum-based decentralized application aiming to bring transparency and trust to P2P lending through Ethereum network smart contracts.
Secure Automated Lending Technology (SALT) allows cryptocurrency asset holders to use their digital assets as collateral for cash loans, without the need to liquidate their holdings, giving rise to a digital-asset-backed lending market.
While blockchain poses a threat to many of the large, centralized banking institutions, some are taking advantage of the new technology to optimize their internal lending, credit scoring, and collateral operations.
In March 2018, ING and Credit Suisse successfully exchanged 25 million euros using HQLA-X, a blockchain-based collateral lending platform.
HQLA-X runs on the R3 Corda blockchain, a platform designed specifically to help heritage financial and commerce institutions migrate away from their inefficient legacy financial infrastructure.
Blockchain and tokenization are going through their own fintech and regulation shakeup right now. In a future blog, I’ll discuss the various efforts to more readily assure smart contracts, and the disruptive business model of security tokens and the US Securities and Exchange Commission.
Parallels to the Global Abundance of Capital
The abundance of capital being created by the advent of P2P loans closely relates to the unprecedented global abundance of capital.
Initial coin offerings (ICOs) and crowdfunding are taking a strong stand in disrupting the $164 billion venture capital market. The total amount invested in ICOs has risen from $6.6 billion in 2017 to $7.15 billion USD in the first half of 2018. Crowdfunding helped projects raise more than $34 billion in 2017, with experts projecting that global crowdfunding investments will reach $300 billion by 2025.
In the last year alone, using ICOs, over a dozen projects have raised hundreds of millions of dollars in mere hours. Take Filecoin, for example, which raised $257 million in only 30 days; its first $135 million was raised in the first hour. Similarly, the Dragon Coin project (which itself is revolutionizing remittance in high-stakes casinos around the world) raised $320 million in its 30-day public ICO.
Some Important Takeaways…
Technology-backed fundraising and financial services are disrupting the world’s largest financial institutions. Anyone, anywhere, at anytime will be able to access the capital they need to pursue their idea.
The speed at which we can go from “I’ve got an idea” to “I run a billion-dollar company” is moving faster than ever.
Following Ray Kurzweil’s Law of Accelerating Returns, the rapid decrease in time to access capital is intimately linked (and greatly dependent on) a financial infrastructure (technology, institutions, platforms, and policies) that can adapt and evolve just as rapidly.
This new abundance of capital requires financial decision-making with ever-higher market prediction precision. That’s exactly where artificial intelligence is already playing a massive role.
Artificial Intelligence, Robo Traders, and Financial Advisors
On May 6, 2010, the Dow Jones Industrial Average suddenly collapsed by 998.5 points (equal to 8 percent, or $1 trillion). The crash lasted over 35 minutes and is now known as the ‘Flash Crash’. While no one knows the specific reason for this 2010 stock market anomaly, experts widely agree that the Flash Crash had to do with algorithmic trading.
With the ability to have instant, trillion-dollar market impacts, algorithmic trading and artificial intelligence are undoubtedly ingrained in how financial markets operate.
In 2017, CNBC.com estimated that 90 percent of daily trading volume in stock trading is done by machine algorithms, and only 10 percent is carried out directly by humans.
Artificial intelligence and financial management algorithms are not only available to top Wall Street players.
Robo-advisor financial management apps, like Wealthfront and Betterment, are rapidly permeating the global market. Wealthfront currently has $9.5 billion in assets under management, and Betterment has $10 billion.
Artificial intelligent financial agents are already helping financial institutions protect your money and fight fraud. A prime application for machine learning is in detecting anomalies in your spending and transaction habits, and flagging potentially fraudulent transactions.
As artificial intelligence continues to exponentially increase in power and capabilities, increasingly powerful trading and financial management bots will come online, finding massive new and previously lost streams of wealth.
How else are artificial intelligence and automation transforming finance?
Disruptive Remittance and Seamless Transactions
When was the last time you paid in cash at a toll booth? How about for a taxi ride?
EZ-Pass, the electronic tolling company implemented extensively on the East Coast, has done wonders to reduce traffic congestion and increase traffic flow.
Driving down I-95 on the East Coast of the United States, drivers rarely notice their financial transaction with the state’s tolling agencies. The transactions are seamless.
The Uber app enables me to travel without my wallet. I can forget about payment on my trip, free up my mental bandwidth and time for higher-priority tasks. The entire process is digitized and, by extension, automated and integrated into Uber’s platform (Note: This incredible convenience many times causes me to accidentally walk out of taxi cabs without paying!).
In January 2018, we saw the success of the first cutting-edge, AI-powered Amazon Go store open in Seattle, Washington. The store marked a new era in remittance and transactions. Gone are the days of carrying credit cards and cash, and gone are the cash registers. And now, on the heals of these early ‘beta-tests’, Amazon is considering opening as many as 3,000 of these cashierless stores by 2023.
Amazon Go stores use AI algorithms that watch various video feeds (from advanced cameras) throughout the store to identify who picks up groceries, exactly what products they select, and how much to charge that person when they walk out of the store. It’s a grab and go experience.
Let’s extrapolate the notion of seamless, integrated payment systems from Amazon Go and Uber’s removal of post-ride payment to the rest of our day-to-day experience.
Imagine this near future:
As you near the front door of your home, your AI assistant summons a self-driving Uber that takes you to the Hyperloop station (after all, you work in L.A. but live in San Francisco).
At the station, you board your pod, without noticing that your ticket purchase was settled via a wireless payment checkpoint.
After work, you stop at the Amazon Go and pick up dinner. Your virtual AI assistant passes your Amazon account information to the store’s payment checkpoint, as the store’s cameras and sensors track you, your cart and charge you auto-magically.
At home, unbeknownst to you, your AI has already restocked your fridge and pantry with whatever items you failed to pick up at the Amazon Go.
Once we remove the actively transacting aspect of finance, what else becomes possible?
Extraordinary transformations are happening in the finance world. We’ve only scratched the surface of the fintech revolution. All of these transformative financial technologies require high-fidelity assurance, robust insurance, and a mechanism for storing value.
I’ll dive into each of these other facets of financial services in future articles.
For now, thanks to coming global communication networks being deployed on 5G, Alphabet’s LUNE, SpaceX’s Starlink and OneWeb, by 2024, nearly all 8 billion people on Earth will be online.
Once connected, these new minds, entrepreneurs, and customers need access to money and financial services to meaningfully participate in the world economy.
By connecting lenders and borrowers around the globe, decentralized lending drives down global interest rates, increases global financial market participation, and enables economic opportunity to the billions of people who are about to come online.
We’re living in the most abundant time in human history, and fintech is just getting started.
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