Tag Archives: emerging technologies

#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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#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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#434492 Black Mirror’s ‘Bandersnatch’ ...

When was the last time you watched a movie where you could control the plot?

Bandersnatch is the first interactive film in the sci fi anthology series Black Mirror. Written by series creator Charlie Brooker and directed by David Slade, the film tells the story of young programmer Stefan Butler, who is adapting a fantasy choose-your-own-adventure novel called Bandersnatch into a video game. Throughout the film, viewers are given the power to influence Butler’s decisions, leading to diverging plots with different endings.

Like many Black Mirror episodes, this film is mind-bending, dark, and thought-provoking. In addition to innovating cinema as we know it, it is a fascinating rumination on free will, parallel realities, and emerging technologies.

Pick Your Own Adventure
With a non-linear script, Bandersnatch is a viewing experience like no other. Throughout the film viewers are given the option of making a decision for the protagonist. In these instances, they have 10 seconds to make a decision until a default decision is made. For example, in the early stage of the plot, Butler is given the choice of accepting or rejecting Tuckersoft’s offer to develop a video game and the viewer gets to decide what he does. The decision then shapes the plot accordingly.

The video game Butler is developing involves moving through a graphical maze of corridors while avoiding a creature called the Pax, and at times making choices through an on-screen instruction (sound familiar?). In other words, it’s a pick-your-own-adventure video game in a pick-your-own-adventure movie.

Many viewers have ended up spending hours exploring all the different branches of the narrative (though the average viewing is 90 minutes). One user on reddit has mapped out an entire flowchart, showing how all the different decisions (and pseudo-decisions) lead to various endings.

However, over time, Butler starts to question his own free will. It’s almost as if he’s beginning to realize that the audience is controlling him. In one branch of the narrative, he is confronted by this reality when the audience indicates to him that he is being controlled in a Netflix show: “I am watching you on Netflix. I make all the decisions for you”. Butler, as you can imagine, is horrified by this message.

But Butler isn’t the only one who has an illusion of choice. We, the seemingly powerful viewers, also appear to operate under the illusion of choice. Despite there being five main endings to the film, they are all more or less the same.

The Science Behind Bandersnatch
The premise of Bandersnatch isn’t based on fantasy, but hard science. Free will has always been a widely-debated issue in neuroscience, with reputable scientists and studies demonstrating that the whole concept may be an illusion.

In the 1970s, a psychologist named Benjamin Libet conducted a series of experiments that studied voluntary decision making in humans. He found that brain activity imitating an action, such as moving your wrist, preceded the conscious awareness of the action.

Psychologist Malcom Gladwell theorizes that while we like to believe we spend a lot of time thinking about our decisions, our mental processes actually work rapidly, automatically, and often subconsciously, from relatively little information. In addition to this, thinking and making decisions are usually a byproduct of several different brain systems, such as the hippocampus, amygdala, and prefrontal cortex working together. You are more conscious of some information processes in the brain than others.

As neuroscientist and philosopher Sam Harris points out in his book Free Will, “You did not pick your parents or the time and place of your birth. You didn’t choose your gender or most of your life experiences. You had no control whatsoever over your genome or the development of your brain. And now your brain is making choices on the basis of preferences and beliefs that have been hammered into it over a lifetime.” Like Butler, we may believe we are operating under full agency of our abilities, but we are at the mercy of many internal and external factors that influence our decisions.

Beyond free will, Bandersnatch also taps into the theory of parallel universes, a facet of the astronomical theory of the multiverse. In astrophysics, there is a theory that there are parallel universes other than our own, where all the choices you made are played out in alternate realities. For instance, if today you had the option of having cereal or eggs for breakfast, and you chose eggs, in a parallel universe, you chose cereal. Human history and our lives may have taken different paths in these parallel universes.

The Future of Cinema
In the future, the viewing experience will no longer be a passive one. Bandersnatch is just a glimpse into how technology is revolutionizing film as we know it and making it a more interactive and personalized experience. All the different scenarios and branches of the plot were scripted and filmed, but in the future, they may be adapted real-time via artificial intelligence.

Virtual reality may allow us to play an even more active role by making us participants or characters in the film. Data from your history of preferences and may be used to create a unique version of the plot that is optimized for your viewing experience.

Let’s also not underestimate the social purpose of advancing film and entertainment. Science fiction gives us the ability to create simulations of the future. Different narratives can allow us to explore how powerful technologies combined with human behavior can result in positive or negative scenarios. Perhaps in the future, science fiction will explore implications of technologies and observe human decision making in novel contexts, via AI-powered films in the virtual world.

Image Credit: andrey_l / Shutterstock.com

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#433895 Sci-Fi Movies Are the Secret Weapon That ...

If there’s one line that stands the test of time in Steven Spielberg’s 1993 classic Jurassic Park, it’s probably Jeff Goldblum’s exclamation, “Your scientists were so preoccupied with whether or not they could, they didn’t stop to think if they should.”

Goldblum’s character, Dr. Ian Malcolm, was warning against the hubris of naively tinkering with dinosaur DNA in an effort to bring these extinct creatures back to life. Twenty-five years on, his words are taking on new relevance as a growing number of scientists and companies are grappling with how to tread the line between “could” and “should” in areas ranging from gene editing and real-world “de-extinction” to human augmentation, artificial intelligence and many others.

Despite growing concerns that powerful emerging technologies could lead to unexpected and wide-ranging consequences, innovators are struggling with how to develop beneficial new products while being socially responsible. Part of the answer could lie in watching more science fiction movies like Jurassic Park.

Hollywood Lessons in Societal Risks
I’ve long been interested in how innovators and others can better understand the increasingly complex landscape around the social risks and benefits associated with emerging technologies. Growing concerns over the impacts of tech on jobs, privacy, security and even the ability of people to live their lives without undue interference highlight the need for new thinking around how to innovate responsibly.

New ideas require creativity and imagination, and a willingness to see the world differently. And this is where science fiction movies can help.

Sci-fi flicks are, of course, notoriously unreliable when it comes to accurately depicting science and technology. But because their plots are often driven by the intertwined relationships between people and technology, they can be remarkably insightful in revealing social factors that affect successful and responsible innovation.

This is clearly seen in Jurassic Park. The movie provides a surprisingly good starting point for thinking about the pros and cons of modern-day genetic engineering and the growing interest in bringing extinct species back from the dead. But it also opens up conversations around the nature of complex systems that involve both people and technology, and the potential dangers of “permissionless” innovation that’s driven by power, wealth and a lack of accountability.

Similar insights emerge from a number of other movies, including Spielberg’s 2002 film “Minority Report”—which presaged a growing capacity for AI-enabled crime prediction and the ethical conundrums it’s raising—as well as the 2014 film Ex Machina.

As with Jurassic Park, Ex Machina centers around a wealthy and unaccountable entrepreneur who is supremely confident in his own abilities. In this case, the technology in question is artificial intelligence.

The movie tells a tale of an egotistical genius who creates a remarkable intelligent machine—but he lacks the awareness to recognize his limitations and the risks of what he’s doing. It also provides a chilling insight into potential dangers of creating machines that know us better than we know ourselves, while not being bound by human norms or values.

The result is a sobering reminder of how, without humility and a good dose of humanity, our innovations can come back to bite us.

The technologies in Jurassic Park, Minority Report, and Ex Machina lie beyond what is currently possible. Yet these films are often close enough to emerging trends that they help reveal the dangers of irresponsible, or simply naive, innovation. This is where these and other science fiction movies can help innovators better understand the social challenges they face and how to navigate them.

Real-World Problems Worked Out On-Screen
In a recent op-ed in the New York Times, journalist Kara Swisher asked, “Who will teach Silicon Valley to be ethical?” Prompted by a growing litany of socially questionable decisions amongst tech companies, Swisher suggests that many of them need to grow up and get serious about ethics. But ethics alone are rarely enough. It’s easy for good intentions to get swamped by fiscal pressures and mired in social realities.

Elon Musk has shown that brilliant tech innovators can take ethical missteps along the way. Image Credit:AP Photo/Chris Carlson
Technology companies increasingly need to find some way to break from business as usual if they are to become more responsible. High-profile cases involving companies like Facebook and Uber as well as Tesla’s Elon Musk have highlighted the social as well as the business dangers of operating without fully understanding the consequences of people-oriented actions.

Many more companies are struggling to create socially beneficial technologies and discovering that, without the necessary insights and tools, they risk blundering about in the dark.

For instance, earlier this year, researchers from Google and DeepMind published details of an artificial intelligence-enabled system that can lip-read far better than people. According to the paper’s authors, the technology has enormous potential to improve the lives of people who have trouble speaking aloud. Yet it doesn’t take much to imagine how this same technology could threaten the privacy and security of millions—especially when coupled with long-range surveillance cameras.

Developing technologies like this in socially responsible ways requires more than good intentions or simply establishing an ethics board. People need a sophisticated understanding of the often complex dynamic between technology and society. And while, as Mozilla’s Mitchell Baker suggests, scientists and technologists engaging with the humanities can be helpful, it’s not enough.

An Easy Way into a Serious Discipline
The “new formulation” of complementary skills Baker says innovators desperately need already exists in a thriving interdisciplinary community focused on socially responsible innovation. My home institution, the School for the Future of Innovation in Society at Arizona State University, is just one part of this.

Experts within this global community are actively exploring ways to translate good ideas into responsible practices. And this includes the need for creative insights into the social landscape around technology innovation, and the imagination to develop novel ways to navigate it.

People love to come together as a movie audience.Image credit: The National Archives UK, CC BY 4.0
Here is where science fiction movies become a powerful tool for guiding innovators, technology leaders and the companies where they work. Their fictional scenarios can reveal potential pitfalls and opportunities that can help steer real-world decisions toward socially beneficial and responsible outcomes, while avoiding unnecessary risks.

And science fiction movies bring people together. By their very nature, these films are social and educational levelers. Look at who’s watching and discussing the latest sci-fi blockbuster, and you’ll often find a diverse cross-section of society. The genre can help build bridges between people who know how science and technology work, and those who know what’s needed to ensure they work for the good of society.

This is the underlying theme in my new book Films from the Future: The Technology and Morality of Sci-Fi Movies. It’s written for anyone who’s curious about emerging trends in technology innovation and how they might potentially affect society. But it’s also written for innovators who want to do the right thing and just don’t know where to start.

Of course, science fiction films alone aren’t enough to ensure socially responsible innovation. But they can help reveal some profound societal challenges facing technology innovators and possible ways to navigate them. And what better way to learn how to innovate responsibly than to invite some friends round, open the popcorn and put on a movie?

It certainly beats being blindsided by risks that, with hindsight, could have been avoided.

Andrew Maynard, Director, Risk Innovation Lab, Arizona State University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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#433798 Five Things We Know About the State of ...

From drug development to food science and genetics, the life sciences industry is alive and innovating in 2018. According to a recent report, emerging technologies offer the most potential for this vital sector. As we enter a ‘fourth industrial revolution’, Artificial Intelligence (AI) and other next-generation technologies are boosting productivity and pushing the boundaries of …

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