Tag Archives: intelligence

#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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Posted in Human Robots

#434559 Can AI Tell the Difference Between a ...

Scarcely a day goes by without another headline about neural networks: some new task that deep learning algorithms can excel at, approaching or even surpassing human competence. As the application of this approach to computer vision has continued to improve, with algorithms capable of specialized recognition tasks like those found in medicine, the software is getting closer to widespread commercial use—for example, in self-driving cars. Our ability to recognize patterns is a huge part of human intelligence: if this can be done faster by machines, the consequences will be profound.

Yet, as ever with algorithms, there are deep concerns about their reliability, especially when we don’t know precisely how they work. State-of-the-art neural networks will confidently—and incorrectly—classify images that look like television static or abstract art as real-world objects like school-buses or armadillos. Specific algorithms could be targeted by “adversarial examples,” where adding an imperceptible amount of noise to an image can cause an algorithm to completely mistake one object for another. Machine learning experts enjoy constructing these images to trick advanced software, but if a self-driving car could be fooled by a few stickers, it might not be so fun for the passengers.

These difficulties are hard to smooth out in large part because we don’t have a great intuition for how these neural networks “see” and “recognize” objects. The main insight analyzing a trained network itself can give us is a series of statistical weights, associating certain groups of points with certain objects: this can be very difficult to interpret.

Now, new research from UCLA, published in the journal PLOS Computational Biology, is testing neural networks to understand the limits of their vision and the differences between computer vision and human vision. Nicholas Baker, Hongjing Lu, and Philip J. Kellman of UCLA, alongside Gennady Erlikhman of the University of Nevada, tested a deep convolutional neural network called VGG-19. This is state-of-the-art technology that is already outperforming humans on standardized tests like the ImageNet Large Scale Visual Recognition Challenge.

They found that, while humans tend to classify objects based on their overall (global) shape, deep neural networks are far more sensitive to the textures of objects, including local color gradients and the distribution of points on the object. This result helps explain why neural networks in image recognition make mistakes that no human ever would—and could allow for better designs in the future.

In the first experiment, a neural network was trained to sort images into 1 of 1,000 different categories. It was then presented with silhouettes of these images: all of the local information was lost, while only the outline of the object remained. Ordinarily, the trained neural net was capable of recognizing these objects, assigning more than 90% probability to the correct classification. Studying silhouettes, this dropped to 10%. While human observers could nearly always produce correct shape labels, the neural networks appeared almost insensitive to the overall shape of the images. On average, the correct object was ranked as the 209th most likely solution by the neural network, even though the overall shapes were an exact match.

A particularly striking example arose when they tried to get the neural networks to classify glass figurines of objects they could already recognize. While you or I might find it easy to identify a glass model of an otter or a polar bear, the neural network classified them as “oxygen mask” and “can opener” respectively. By presenting glass figurines, where the texture information that neural networks relied on for classifying objects is lost, the neural network was unable to recognize the objects by shape alone. The neural network was similarly hopeless at classifying objects based on drawings of their outline.

If you got one of these right, you’re better than state-of-the-art image recognition software. Image Credit: Nicholas Baker, Hongjing Lu, Gennady Erlikhman, Philip J. Kelman. “Deep convolutional networks do not classify based on global object shape.” Plos Computational Biology. 12/7/18. / CC BY 4.0
When the neural network was explicitly trained to recognize object silhouettes—given no information in the training data aside from the object outlines—the researchers found that slight distortions or “ripples” to the contour of the image were again enough to fool the AI, while humans paid them no mind.

The fact that neural networks seem to be insensitive to the overall shape of an object—relying instead on statistical similarities between local distributions of points—suggests a further experiment. What if you scrambled the images so that the overall shape was lost but local features were preserved? It turns out that the neural networks are far better and faster at recognizing scrambled versions of objects than outlines, even when humans struggle. Students could classify only 37% of the scrambled objects, while the neural network succeeded 83% of the time.

Humans vastly outperform machines at classifying object (a) as a bear, while the machine learning algorithm has few problems classifying the bear in figure (b). Image Credit: Nicholas Baker, Hongjing Lu, Gennady Erlikhman, Philip J. Kelman. “Deep convolutional networks do not classify based on global object shape.” Plos Computational Biology. 12/7/18. / CC BY 4.0
“This study shows these systems get the right answer in the images they were trained on without considering shape,” Kellman said. “For humans, overall shape is primary for object recognition, and identifying images by overall shape doesn’t seem to be in these deep learning systems at all.”

Naively, one might expect that—as the many layers of a neural network are modeled on connections between neurons in the brain and resemble the visual cortex specifically—the way computer vision operates must necessarily be similar to human vision. But this kind of research shows that, while the fundamental architecture might resemble that of the human brain, the resulting “mind” operates very differently.

Researchers can, increasingly, observe how the “neurons” in neural networks light up when exposed to stimuli and compare it to how biological systems respond to the same stimuli. Perhaps someday it might be possible to use these comparisons to understand how neural networks are “thinking” and how those responses differ from humans.

But, as yet, it takes a more experimental psychology to probe how neural networks and artificial intelligence algorithms perceive the world. The tests employed against the neural network are closer to how scientists might try to understand the senses of an animal or the developing brain of a young child rather than a piece of software.

By combining this experimental psychology with new neural network designs or error-correction techniques, it may be possible to make them even more reliable. Yet this research illustrates just how much we still don’t understand about the algorithms we’re creating and using: how they tick, how they make decisions, and how they’re different from us. As they play an ever-greater role in society, understanding the psychology of neural networks will be crucial if we want to use them wisely and effectively—and not end up missing the woods for the trees.

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#434544 This Week’s Awesome Stories From ...

ARTIFICIAL INTELLIGENCE
DeepMind Beats Pros at Starcraft in Another Triumph for Bots
Tom Simonite | Wired
“DeepMind’s feat is the most complex yet in a long train of contests in which computers have beaten top humans at games. Checkers fell in 1994, chess in 1997, and DeepMind’s earlier bot AlphaGo became the first to beat a champion at the board game Go in 2016. The StarCraft bot is the most powerful AI game player yet; it may also be the least unexpected.”

GENETICS
Complete Axolotl Genome Could Pave the Way Toward Human Tissue Regeneration
George Dvorsky | Gizmodo
“Now that researchers have a near-complete axolotl genome—the new assembly still requires a bit of fine-tuning (more on that in a bit)—they, along with others, can now go about the work of identifying the genes responsible for axolotl tissue regeneration.”

FUTURE
We Analyzed 16,625 Papers to Figure Out Where AI Is Headed Next
Karen Hao | MIT Technology Review
“…though deep learning has singlehandedly thrust AI into the public eye, it represents just a small blip in the history of humanity’s quest to replicate our own intelligence. It’s been at the forefront of that effort for less than 10 years. When you zoom out on the whole history of the field, it’s easy to realize that it could soon be on its way out.”

COMPUTING
Apple’s Finger-Controller Patent Is a Glimpse at Mixed Reality’s Future
Mark Sullivan | Fast Company
“[Apple’s] engineers are now looking past the phone touchscreen toward mixed reality, where the company’s next great UX will very likely be built. A recent patent application gives some tantalizing clues as to how Apple’s people are thinking about aspects of that challenge.”

GOVERNANCE
How Do You Govern Machines That Can Learn? Policymakers Are Trying to Figure That Out
Steve Lohr | The New York Times
“Regulation is coming. That’s a good thing. Rules of competition and behavior are the foundation of healthy, growing markets. That was the consensus of the policymakers at MIT. But they also agreed that artificial intelligence raises some fresh policy challenges.”

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Posted in Human Robots

#434534 To Extend Our Longevity, First We Must ...

Healthcare today is reactive, retrospective, bureaucratic, and expensive. It’s sick care, not healthcare.

But that is radically changing at an exponential rate.

Through this multi-part blog series on longevity, I’ll take a deep dive into aging, longevity, and healthcare technologies that are working together to dramatically extend the human lifespan, disrupting the $3 trillion healthcare system in the process.

I’ll begin the series by explaining the nine hallmarks of aging, as explained in this journal article. Next, I’ll break down the emerging technologies and initiatives working to combat these nine hallmarks. Finally, I’ll explore the transformative implications of dramatically extending the human health span.

In this blog I’ll cover:

Why the healthcare system is broken
Why, despite this, we live in the healthiest time in human history
The nine mechanisms of aging

Let’s dive in.

The System is Broken—Here’s the Data:

Doctors spend $210 billion per year on procedures that aren’t based on patient need, but fear of liability.
Americans spend, on average, $8,915 per person on healthcare—more than any other country on Earth.
Prescription drugs cost around 50 percent more in the US than in other industrialized countries.
At current rates, by 2025, nearly 25 percent of the US GDP will be spent on healthcare.
It takes 12 years and $359 million, on average, to take a new drug from the lab to a patient.
Only 5 in 5,000 of these new drugs proceed to human testing. From there, only 1 of those 5 is actually approved for human use.

And Yet, We Live in the Healthiest Time in Human History
Consider these insights, which I adapted from Max Roser’s excellent database Our World in Data:

Right now, the countries with the lowest life expectancy in the world still have higher life expectancies than the countries with the highest life expectancy did in 1800.
In 1841, a 5-year-old had a life expectancy of 55 years. Today, a 5-year-old can expect to live 82 years—an increase of 27 years.
We’re seeing a dramatic increase in healthspan. In 1845, a newborn would expect to live to 40 years old. For a 70-year-old, that number became 79. Now, people of all ages can expect to live to be 81 to 86 years old.
100 years ago, 1 of 3 children would die before the age of 5. As of 2015, the child mortality rate fell to just 4.3 percent.
The cancer mortality rate has declined 27 percent over the past 25 years.

Figure: Around the globe, life expectancy has doubled since the 1800s. | Image from Life Expectancy by Max Roser – Our World in Data / CC BY SA
Figure: A dramatic reduction in child mortality in 1800 vs. in 2015. | Image from Child Mortality by Max Roser – Our World in Data / CC BY SA
The 9 Mechanisms of Aging
*This section was adapted from CB INSIGHTS: The Future Of Aging.

Longevity, healthcare, and aging are intimately linked.

With better healthcare, we can better treat some of the leading causes of death, impacting how long we live.

By investigating how to treat diseases, we’ll inevitably better understand what causes these diseases in the first place, which directly correlates to why we age.

Following are the nine hallmarks of aging. I’ll share examples of health and longevity technologies addressing each of these later in this blog series.

Genomic instability: As we age, the environment and normal cellular processes cause damage to our genes. Activities like flying at high altitude, for example, expose us to increased radiation or free radicals. This damage compounds over the course of life and is known to accelerate aging.
Telomere attrition: Each strand of DNA in the body (known as chromosomes) is capped by telomeres. These short snippets of DNA repeated thousands of times are designed to protect the bulk of the chromosome. Telomeres shorten as our DNA replicates; if a telomere reaches a certain critical shortness, a cell will stop dividing, resulting in increased incidence of disease.
Epigenetic alterations: Over time, environmental factors will change how genes are expressed, i.e., how certain sequences of DNA are read and the instruction set implemented.
Loss of proteostasis: Over time, different proteins in our body will no longer fold and function as they are supposed to, resulting in diseases ranging from cancer to neurological disorders.
Deregulated nutrient-sensing: Nutrient levels in the body can influence various metabolic pathways. Among the affected parts of these pathways are proteins like IGF-1, mTOR, sirtuins, and AMPK. Changing levels of these proteins’ pathways has implications on longevity.
Mitochondrial dysfunction: Mitochondria (our cellular power plants) begin to decline in performance as we age. Decreased performance results in excess fatigue and other symptoms of chronic illnesses associated with aging.
Cellular senescence: As cells age, they stop dividing and cannot be removed from the body. They build up and typically cause increased inflammation.
Stem cell exhaustion: 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 the body.
Altered intercellular communication: The communication mechanisms that cells use are disrupted as cells age, resulting in decreased ability to transmit information between cells.

Conclusion
Over the past 200 years, we have seen an abundance of healthcare technologies enable a massive lifespan boom.

Now, exponential technologies like artificial intelligence, 3D printing and sensors, as well as tremendous advancements in genomics, stem cell research, chemistry, and many other fields, are beginning to tackle the fundamental issues of why we age.

In the next blog in this series, we will dive into how genome sequencing and editing, along with new classes of drugs, are augmenting our biology to further extend our healthy lives.

What will you be able to achieve with an extra 30 to 50 healthy years (or longer) in your lifespan? Personally, I’m excited for a near-infinite lifespan to take on moonshots.

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#434532 How Microrobots Will Fix Our Roads and ...

Swarms of microrobots will scuttle along beneath our roads and pavements, finding and fixing leaky pipes and faulty cables. Thanks to their efforts, we can avoid costly road work that costs billions of dollars each year—not to mention frustrating traffic delays.

That is, if a new project sponsored by the U.K. government is a success. Recent developments in the space seem to point towards a bright future for microrobots.

Microrobots Saving Billions
Each year, around 1.5 million road excavations take place across the U.K. Many are due to leaky pipes and faulty cables that necessitate excavation of road surfaces in order to fix them. The resulting repairs, alongside disruptions to traffic and businesses, are estimated to cost a whopping £6.3 billion ($8 billion).

A consortium of scientists, led by University of Sheffield Professor Kirill Horoshenkov, are planning to use microrobots to negate most of these costs. The group has received a £7.2 million ($9.2 million) grant to develop and build their bots.

According to Horoshenkov, the microrobots will come in two versions. One is an inspection bot, which will navigate along underground infrastructure and examine its condition via sonar. The inspectors will be complemented by worker bots capable of carrying out repairs with cement and adhesives or cleaning out blockages with a high-powered jet. The inspector bots will be around one centimeter long and possibly autonomous, while the worker bots will be slightly larger and steered via remote control.

If successful, it is believed the bots could potentially save the U.K. economy around £5 billion ($6.4 billion) a year.

The U.K. government has set aside a further £19 million ($24 million) for research into robots for hazardous environments, such as nuclear decommissioning, drones for oil pipeline monitoring, and artificial intelligence software to detect the need for repairs on satellites in orbit.

The Lowest-Hanging Fruit
Microrobots like the ones now under development in the U.K. have many potential advantages and use cases. Thanks to their small size they can navigate tight spaces, for example in search and rescue operations, and robot swarm technology would allow them to collaborate to perform many different functions, including in construction projects.

To date, the number of microrobots in use is relatively limited, but that could be about to change, with bots closing in on other types of inspection jobs, which could be considered one of the lowest-hanging fruits.

Engineering firm Rolls-Royce (not the car company, but the one that builds aircraft engines) is looking to use microrobots to inspect some of the up to 25,000 individual parts that make up an engine. The microrobots use the cockroach as a model, and Rolls Royce believes they could save engineers time when performing the maintenance checks that can take over a month per engine.

Even Smaller Successes
Going further down in scale, recent years have seen a string of successes for nanobots. For example, a team of researchers at the Femto-ST Institute have used nanobots to build what is likely the world’s smallest house (if this isn’t a category at Guinness, someone needs to get on the phone with them), which stands a ‘towering’ 0.015 millimeters.

One of the areas where nanobots have shown great promise is in medicine. Several studies have shown how the minute bots are capable of delivering drugs directly into dense biological tissue, which can otherwise be highly challenging to target directly. Such delivery systems have a great potential for improving the treatment of a wide range of ailments and illnesses, including cancer.

There’s no question that the ecosystem of microrobots and nanobots is evolving. While still in their early days, the above successes point to a near-future boom in the bots we may soon refer to as our ‘littlest everyday helpers.’

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