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#435098 Coming of Age in the Age of AI: The ...

The first generation to grow up entirely in the 21st century will never remember a time before smartphones or smart assistants. They will likely be the first children to ride in self-driving cars, as well as the first whose healthcare and education could be increasingly turned over to artificially intelligent machines.

Futurists, demographers, and marketers have yet to agree on the specifics of what defines the next wave of humanity to follow Generation Z. That hasn’t stopped some, like Australian futurist Mark McCrindle, from coining the term Generation Alpha, denoting a sort of reboot of society in a fully-realized digital age.

“In the past, the individual had no power, really,” McCrindle told Business Insider. “Now, the individual has great control of their lives through being able to leverage this world. Technology, in a sense, transformed the expectations of our interactions.”

No doubt technology may impart Marvel superhero-like powers to Generation Alpha that even tech-savvy Millennials never envisioned over cups of chai latte. But the powers of machine learning, computer vision, and other disciplines under the broad category of artificial intelligence will shape this yet unformed generation more definitively than any before it.

What will it be like to come of age in the Age of AI?

The AI Doctor Will See You Now
Perhaps no other industry is adopting and using AI as much as healthcare. The term “artificial intelligence” appears in nearly 90,000 publications from biomedical literature and research on the PubMed database.

AI is already transforming healthcare and longevity research. Machines are helping to design drugs faster and detect disease earlier. And AI may soon influence not only how we diagnose and treat illness in children, but perhaps how we choose which children will be born in the first place.

A study published earlier this month in NPJ Digital Medicine by scientists from Weill Cornell Medicine used 12,000 photos of human embryos taken five days after fertilization to train an AI algorithm on how to tell which in vitro fertilized embryo had the best chance of a successful pregnancy based on its quality.

Investigators assigned each embryo a grade based on various aspects of its appearance. A statistical analysis then correlated that grade with the probability of success. The algorithm, dubbed Stork, was able to classify the quality of a new set of images with 97 percent accuracy.

“Our algorithm will help embryologists maximize the chances that their patients will have a single healthy pregnancy,” said Dr. Olivier Elemento, director of the Caryl and Israel Englander Institute for Precision Medicine at Weill Cornell Medicine, in a press release. “The IVF procedure will remain the same, but we’ll be able to improve outcomes by harnessing the power of artificial intelligence.”

Other medical researchers see potential in applying AI to detect possible developmental issues in newborns. Scientists in Europe, working with a Finnish AI startup that creates seizure monitoring technology, have developed a technique for detecting movement patterns that might indicate conditions like cerebral palsy.

Published last month in the journal Acta Pediatrica, the study relied on an algorithm to extract the movements from a newborn, turning it into a simplified “stick figure” that medical experts could use to more easily detect clinically relevant data.

The researchers are continuing to improve the datasets, including using 3D video recordings, and are now developing an AI-based method for determining if a child’s motor maturity aligns with its true age. Meanwhile, a study published in February in Nature Medicine discussed the potential of using AI to diagnose pediatric disease.

AI Gets Classy
After being weaned on algorithms, Generation Alpha will hit the books—about machine learning.

China is famously trying to win the proverbial AI arms race by spending billions on new technologies, with one Chinese city alone pledging nearly $16 billion to build a smart economy based on artificial intelligence.

To reach dominance by its stated goal of 2030, Chinese cities are also incorporating AI education into their school curriculum. Last year, China published its first high school textbook on AI, according to the South China Morning Post. More than 40 schools are participating in a pilot program that involves SenseTime, one of the country’s biggest AI companies.

In the US, where it seems every child has access to their own AI assistant, researchers are just beginning to understand how the ubiquity of intelligent machines will influence the ways children learn and interact with their highly digitized environments.

Sandra Chang-Kredl, associate professor of the department of education at Concordia University, told The Globe and Mail that AI could have detrimental effects on learning creativity or emotional connectedness.

Similar concerns inspired Stefania Druga, a member of the Personal Robots group at the MIT Media Lab (and former Education Teaching Fellow at SU), to study interactions between children and artificial intelligence devices in order to encourage positive interactions.

Toward that goal, Druga created Cognimates, a platform that enables children to program and customize their own smart devices such as Alexa or even a smart, functional robot. The kids can also use Cognimates to train their own AI models or even build a machine learning version of Rock Paper Scissors that gets better over time.

“I believe it’s important to also introduce young people to the concepts of AI and machine learning through hands-on projects so they can make more informed and critical use of these technologies,” Druga wrote in a Medium blog post.

Druga is also the founder of Hackidemia, an international organization that sponsors workshops and labs around the world to introduce kids to emerging technologies at an early age.

“I think we are in an arms race in education with the advancement of technology, and we need to start thinking about AI literacy before patterns of behaviors for children and their families settle in place,” she wrote.

AI Goes Back to School
It also turns out that AI has as much to learn from kids. More and more researchers are interested in understanding how children grasp basic concepts that still elude the most advanced machine minds.

For example, developmental psychologist Alison Gopnik has written and lectured extensively about how studying the minds of children can provide computer scientists clues on how to improve machine learning techniques.

In an interview on Vox, she described that while DeepMind’s AlpahZero was trained to be a chessmaster, it struggles with even the simplest changes in the rules, such as allowing the bishop to move horizontally instead of vertically.

“A human chess player, even a kid, will immediately understand how to transfer that new rule to their playing of the game,” she noted. “Flexibility and generalization are something that even human one-year-olds can do but that the best machine learning systems have a much harder time with.”

Last year, the federal defense agency DARPA announced a new program aimed at improving AI by teaching it “common sense.” One of the chief strategies is to develop systems for “teaching machines through experience, mimicking the way babies grow to understand the world.”

Such an approach is also the basis of a new AI program at MIT called the MIT Quest for Intelligence.

The research leverages cognitive science to understand human intelligence, according to an article on the project in MIT Technology Review, such as exploring how young children visualize the world using their own innate 3D models.

“Children’s play is really serious business,” said Josh Tenenbaum, who leads the Computational Cognitive Science lab at MIT and his head of the new program. “They’re experiments. And that’s what makes humans the smartest learners in the known universe.”

In a world increasingly driven by smart technologies, it’s good to know the next generation will be able to keep up.

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Posted in Human Robots

#434857 It’s 2019 – where’s my ...

I loved the “Thundercats” cartoon as a child, watching cat-like humanoids fighting the forces of evil. Whenever their leader was in trouble, he'd unleash the Sword of Omens to gain “sight beyond sight,” the ability to see events happening at faraway places, or bellow “Thunder, Thunder, Thunder, Thundercats, Hooo!” to instantaneously summon his allies to his location to join the fight. What kid didn't want those superpowers? 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

#434701 3 Practical Solutions to Offset ...

In recent years, the media has sounded the alarm about mass job loss to automation and robotics—some studies predict that up to 50 percent of current jobs or tasks could be automated in coming decades. While this topic has received significant attention, much of the press focuses on potential problems without proposing realistic solutions or considering new opportunities.

The economic impacts of AI, robotics, and automation are complex topics that require a more comprehensive perspective to understand. Is universal basic income, for example, the answer? Many believe so, and there are a number of experiments in progress. But it’s only one strategy, and without a sustainable funding source, universal basic income may not be practical.

As automation continues to accelerate, we’ll need a multi-pronged approach to ease the transition. In short, we need to update broad socioeconomic strategies for a new century of rapid progress. How, then, do we plan practical solutions to support these new strategies?

Take history as a rough guide to the future. Looking back, technology revolutions have three themes in common.

First, past revolutions each produced profound benefits to productivity, increasing human welfare. Second, technological innovation and technology diffusion have accelerated over time, each iteration placing more strain on the human ability to adapt. And third, machines have gradually replaced more elements of human work, with human societies adapting by moving into new forms of work—from agriculture to manufacturing to service, for example.

Public and private solutions, therefore, need to be developed to address each of these three components of change. Let’s explore some practical solutions for each in turn.

Figure 1. Technology’s structural impacts in the 21st century. Refer to Appendix I for quantitative charts and technological examples corresponding to the numbers (1-22) in each slice.
Solution 1: Capture New Opportunities Through Aggressive Investment
The rapid emergence of new technology promises a bounty of opportunity for the twenty-first century’s economic winners. This technological arms race is shaping up to be a global affair, and the winners will be determined in part by who is able to build the future economy fastest and most effectively. Both the private and public sectors have a role to play in stimulating growth.

At the country level, several nations have created competitive strategies to promote research and development investments as automation technologies become more mature.

Germany and China have two of the most notable growth strategies. Germany’s Industrie 4.0 plan targets a 50 percent increase in manufacturing productivity via digital initiatives, while halving the resources required. China’s Made in China 2025 national strategy sets ambitious targets and provides subsidies for domestic innovation and production. It also includes building new concept cities, investing in robotics capabilities, and subsidizing high-tech acquisitions abroad to become the leader in certain high-tech industries. For China, specifically, tech innovation is driven partially by a fear that technology will disrupt social structures and government control.

Such opportunities are not limited to existing economic powers. Estonia’s progress after the breakup of the Soviet Union is a good case study in transitioning to a digital economy. The nation rapidly implemented capitalistic reforms and transformed itself into a technology-centric economy in preparation for a massive tech disruption. Internet access was declared a right in 2000, and the country’s classrooms were outfitted for a digital economy, with coding as a core educational requirement starting at kindergarten. Internet broadband speeds in Estonia are among the fastest in the world. Accordingly, the World Bank now ranks Estonia as a high-income country.

Solution 2: Address Increased Rate of Change With More Nimble Education Systems
Education and training are currently not set for the speed of change in the modern economy. Schools are still based on a one-time education model, with school providing the foundation for a single lifelong career. With content becoming obsolete faster and rapidly escalating costs, this system may be unsustainable in the future. To help workers more smoothly transition from one job into another, for example, we need to make education a more nimble, lifelong endeavor.

Primary and university education may still have a role in training foundational thinking and general education, but it will be necessary to curtail rising price of tuition and increase accessibility. Massive open online courses (MooCs) and open-enrollment platforms are early demonstrations of what the future of general education may look like: cheap, effective, and flexible.

Georgia Tech’s online Engineering Master’s program (a fraction of the cost of residential tuition) is an early example in making university education more broadly available. Similarly, nanodegrees or microcredentials provided by online education platforms such as Udacity and Coursera can be used for mid-career adjustments at low cost. AI itself may be deployed to supplement the learning process, with applications such as AI-enhanced tutorials or personalized content recommendations backed by machine learning. Recent developments in neuroscience research could optimize this experience by perfectly tailoring content and delivery to the learner’s brain to maximize retention.

Finally, companies looking for more customized skills may take a larger role in education, providing on-the-job training for specific capabilities. One potential model involves partnering with community colleges to create apprenticeship-style learning, where students work part-time in parallel with their education. Siemens has pioneered such a model in four states and is developing a playbook for other companies to do the same.

Solution 3: Enhance Social Safety Nets to Smooth Automation Impacts
If predicted job losses to automation come to fruition, modernizing existing social safety nets will increasingly become a priority. While the issue of safety nets can become quickly politicized, it is worth noting that each prior technological revolution has come with corresponding changes to the social contract (see below).

The evolving social contract (U.S. examples)
– 1842 | Right to strike
– 1924 | Abolish child labor
– 1935 | Right to unionize
– 1938 | 40-hour work week
– 1962, 1974 | Trade adjustment assistance
– 1964 | Pay discrimination prohibited
– 1970 | Health and safety laws
– 21st century | AI and automation adjustment assistance?

Figure 2. Labor laws have historically adjusted as technology and society progressed

Solutions like universal basic income (no-strings-attached monthly payout to all citizens) are appealing in concept, but somewhat difficult to implement as a first measure in countries such as the US or Japan that already have high debt. Additionally, universal basic income may create dis-incentives to stay in the labor force. A similar cautionary tale in program design was the Trade Adjustment Assistance (TAA), which was designed to protect industries and workers from import competition shocks from globalization, but is viewed as a missed opportunity due to insufficient coverage.

A near-term solution could come in the form of graduated wage insurance (compensation for those forced to take a lower-paying job), including health insurance subsidies to individuals directly impacted by automation, with incentives to return to the workforce quickly. Another topic to tackle is geographic mismatch between workers and jobs, which can be addressed by mobility assistance. Lastly, a training stipend can be issued to individuals as means to upskill.

Policymakers can intervene to reverse recent historical trends that have shifted incomes from labor to capital owners. The balance could be shifted back to labor by placing higher taxes on capital—an example is the recently proposed “robot tax” where the taxation would be on the work rather than the individual executing it. That is, if a self-driving car performs the task that formerly was done by a human, the rideshare company will still pay the tax as if a human was driving.

Other solutions may involve distribution of work. Some countries, such as France and Sweden, have experimented with redistributing working hours. The idea is to cap weekly hours, with the goal of having more people employed and work more evenly spread. So far these programs have had mixed results, with lower unemployment but high costs to taxpayers, but are potential models that can continue to be tested.

We cannot stop growth, nor should we. With the roles in response to this evolution shifting, so should the social contract between the stakeholders. Government will continue to play a critical role as a stabilizing “thumb” in the invisible hand of capitalism, regulating and cushioning against extreme volatility, particularly in labor markets.

However, we already see business leaders taking on some of the role traditionally played by government—thinking about measures to remedy risks of climate change or economic proposals to combat unemployment—in part because of greater agility in adapting to change. Cross-disciplinary collaboration and creative solutions from all parties will be critical in crafting the future economy.

Note: The full paper this article is based on is available here.

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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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