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#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
#434260 The Most Surprising Tech Breakthroughs ...
Development across the entire information technology landscape certainly didn’t slow down this year. From CRISPR babies, to the rapid decline of the crypto markets, to a new robot on Mars, and discovery of subatomic particles that could change modern physics as we know it, there was no shortage of headline-grabbing breakthroughs and discoveries.
As 2018 comes to a close, we can pause and reflect on some of the biggest technology breakthroughs and scientific discoveries that occurred this year.
I reached out to a few Singularity University speakers and faculty across the various technology domains we cover asking what they thought the biggest breakthrough was in their area of expertise. The question posed was:
“What, in your opinion, was the biggest development in your area of focus this year? Or, what was the breakthrough you were most surprised by in 2018?”
I can share that for me, hands down, the most surprising development I came across in 2018 was learning that a publicly-traded company that was briefly valued at over $1 billion, and has over 12,000 employees and contractors spread around the world, has no physical office space and the entire business is run and operated from inside an online virtual world. This is Ready Player One stuff happening now.
For the rest, here’s what our experts had to say.
DIGITAL BIOLOGY
Dr. Tiffany Vora | Faculty Director and Vice Chair, Digital Biology and Medicine, Singularity University
“That’s easy: CRISPR babies. I knew it was technically possible, and I’ve spent two years predicting it would happen first in China. I knew it was just a matter of time but I failed to predict the lack of oversight, the dubious consent process, the paucity of publicly-available data, and the targeting of a disease that we already know how to prevent and treat and that the children were at low risk of anyway.
I’m not convinced that this counts as a technical breakthrough, since one of the girls probably isn’t immune to HIV, but it sure was a surprise.”
For more, read Dr. Vora’s summary of this recent stunning news from China regarding CRISPR-editing human embryos.
QUANTUM COMPUTING
Andrew Fursman | Co-Founder/CEO 1Qbit, Faculty, Quantum Computing, Singularity University
“There were two last-minute holiday season surprise quantum computing funding and technology breakthroughs:
First, right before the government shutdown, one priority legislative accomplishment will provide $1.2 billion in quantum computing research over the next five years. Second, there’s the rise of ions as a truly viable, scalable quantum computing architecture.”
*Read this Gizmodo profile on an exciting startup in the space to learn more about this type of quantum computing
ENERGY
Ramez Naam | Chair, Energy and Environmental Systems, Singularity University
“2018 had plenty of energy surprises. In solar, we saw unsubsidized prices in the sunny parts of the world at just over two cents per kwh, or less than half the price of new coal or gas electricity. In the US southwest and Texas, new solar is also now cheaper than new coal or gas. But even more shockingly, in Germany, which is one of the least sunny countries on earth (it gets less sunlight than Canada) the average bid for new solar in a 2018 auction was less than 5 US cents per kwh. That’s as cheap as new natural gas in the US, and far cheaper than coal, gas, or any other new electricity source in most of Europe.
In fact, it’s now cheaper in some parts of the world to build new solar or wind than to run existing coal plants. Think tank Carbon Tracker calculates that, over the next 10 years, it will become cheaper to build new wind or solar than to operate coal power in most of the world, including specifically the US, most of Europe, and—most importantly—India and the world’s dominant burner of coal, China.
Here comes the sun.”
GLOBAL GRAND CHALLENGES
Darlene Damm | Vice Chair, Faculty, Global Grand Challenges, Singularity University
“In 2018 we saw a lot of areas in the Global Grand Challenges move forward—advancements in robotic farming technology and cultured meat, low-cost 3D printed housing, more sophisticated types of online education expanding to every corner of the world, and governments creating new policies to deal with the ethics of the digital world. These were the areas we were watching and had predicted there would be change.
What most surprised me was to see young people, especially teenagers, start to harness technology in powerful ways and use it as a platform to make their voices heard and drive meaningful change in the world. In 2018 we saw teenagers speak out on a number of issues related to their well-being and launch digital movements around issues such as gun and school safety, global warming and environmental issues. We often talk about the harm technology can cause to young people, but on the flip side, it can be a very powerful tool for youth to start changing the world today and something I hope we see more of in the future.”
BUSINESS STRATEGY
Pascal Finette | Chair, Entrepreneurship and Open Innovation, Singularity University
“Without a doubt the rapid and massive adoption of AI, specifically deep learning, across industries, sectors, and organizations. What was a curiosity for most companies at the beginning of the year has quickly made its way into the boardroom and leadership meetings, and all the way down into the innovation and IT department’s agenda. You are hard-pressed to find a mid- to large-sized company today that is not experimenting or implementing AI in various aspects of its business.
On the slightly snarkier side of answering this question: The very rapid decline in interest in blockchain (and cryptocurrencies). The blockchain party was short, ferocious, and ended earlier than most would have anticipated, with a huge hangover for some. The good news—with the hot air dissipated, we can now focus on exploring the unique use cases where blockchain does indeed offer real advantages over centralized approaches.”
*Author note: snark is welcome and appreciated
ROBOTICS
Hod Lipson | Director, Creative Machines Lab, Columbia University
“The biggest surprise for me this year in robotics was learning dexterity. For decades, roboticists have been trying to understand and imitate dexterous manipulation. We humans seem to be able to manipulate objects with our fingers with incredible ease—imagine sifting through a bunch of keys in the dark, or tossing and catching a cube. And while there has been much progress in machine perception, dexterous manipulation remained elusive.
There seemed to be something almost magical in how we humans can physically manipulate the physical world around us. Decades of research in grasping and manipulation, and millions of dollars spent on robot-hand hardware development, has brought us little progress. But in late 2018, the Berkley OpenAI group demonstrated that this hurdle may finally succumb to machine learning as well. Given 200 years worth of practice, machines learned to manipulate a physical object with amazing fluidity. This might be the beginning of a new age for dexterous robotics.”
MACHINE LEARNING
Jeremy Howard | Founding Researcher, fast.ai, Founder/CEO, Enlitic, Faculty Data Science, Singularity University
“The biggest development in machine learning this year has been the development of effective natural language processing (NLP).
The New York Times published an article last month titled “Finally, a Machine That Can Finish Your Sentence,” which argued that NLP neural networks have reached a significant milestone in capability and speed of development. The “finishing your sentence” capability mentioned in the title refers to a type of neural network called a “language model,” which is literally a model that learns how to finish your sentences.
Earlier this year, two systems (one, called ELMO, is from the Allen Institute for AI, and the other, called ULMFiT, was developed by me and Sebastian Ruder) showed that such a model could be fine-tuned to dramatically improve the state-of-the-art in nearly every NLP task that researchers study. This work was further developed by OpenAI, which in turn was greatly scaled up by Google Brain, who created a system called BERT which reached human-level performance on some of NLP’s toughest challenges.
Over the next year, expect to see fine-tuned language models used for everything from understanding medical texts to building disruptive social media troll armies.”
DIGITAL MANUFACTURING
Andre Wegner | Founder/CEO Authentise, Chair, Digital Manufacturing, Singularity University
“Most surprising to me was the extent and speed at which the industry finally opened up.
While previously, only few 3D printing suppliers had APIs and knew what to do with them, 2018 saw nearly every OEM (or original equipment manufacturer) enabling data access and, even more surprisingly, shying away from proprietary standards and adopting MTConnect, as stalwarts such as 3D Systems and Stratasys have been. This means that in two to three years, data access to machines will be easy, commonplace, and free. The value will be in what is being done with that data.
Another example of this openness are the seemingly endless announcements of integrated workflows: GE’s announcement with most major software players to enable integrated solutions, EOS’s announcement with Siemens, and many more. It’s clear that all actors in the additive ecosystem have taken a step forward in terms of openness. The result is a faster pace of innovation, particularly in the software and data domains that are crucial to enabling comprehensive digital workflow to drive agile and resilient manufacturing.
I’m more optimistic we’ll achieve that now than I was at the end of 2017.”
SCIENCE AND DISCOVERY
Paul Saffo | Chair, Future Studies, Singularity University, Distinguished Visiting Scholar, Stanford Media-X Research Network
“The most important development in technology this year isn’t a technology, but rather the astonishing science surprises made possible by recent technology innovations. My short list includes the discovery of the “neptmoon”, a Neptune-scale moon circling a Jupiter-scale planet 8,000 lightyears from us; the successful deployment of the Mars InSight Lander a month ago; and the tantalizing ANITA detection (what could be a new subatomic particle which would in turn blow the standard model wide open). The highest use of invention is to support science discovery, because those discoveries in turn lead us to the future innovations that will improve the state of the world—and fire up our imaginations.”
ROBOTICS
Pablos Holman | Inventor, Hacker, Faculty, Singularity University
“Just five or ten years ago, if you’d asked any of us technologists “What is harder for robots? Eyes, or fingers?” We’d have all said eyes. Robots have extraordinary eyes now, but even in a surgical robot, the fingers are numb and don’t feel anything. Stanford robotics researchers have invented fingertips that can feel, and this will be a kingpin that allows robots to go everywhere they haven’t been yet.”
BLOCKCHAIN
Nathana Sharma | Blockchain, Policy, Law, and Ethics, Faculty, Singularity University
“2017 was the year of peak blockchain hype. 2018 has been a year of resetting expectations and technological development, even as the broader cryptocurrency markets have faced a winter. It’s now about seeing adoption and applications that people want and need to use rise. An incredible piece of news from December 2018 is that Facebook is developing a cryptocurrency for users to make payments through Whatsapp. That’s surprisingly fast mainstream adoption of this new technology, and indicates how powerful it is.”
ARTIFICIAL INTELLIGENCE
Neil Jacobstein | Chair, Artificial Intelligence and Robotics, Singularity University
“I think one of the most visible improvements in AI was illustrated by the Boston Dynamics Parkour video. This was not due to an improvement in brushless motors, accelerometers, or gears. It was due to improvements in AI algorithms and training data. To be fair, the video released was cherry-picked from numerous attempts, many of which ended with a crash. However, the fact that it could be accomplished at all in 2018 was a real win for both AI and robotics.”
NEUROSCIENCE
Divya Chander | Chair, Neuroscience, Singularity University
“2018 ushered in a new era of exponential trends in non-invasive brain modulation. Changing behavior or restoring function takes on a new meaning when invasive interfaces are no longer needed to manipulate neural circuitry. The end of 2018 saw two amazing announcements: the ability to grow neural organoids (mini-brains) in a dish from neural stem cells that started expressing electrical activity, mimicking the brain function of premature babies, and the first (known) application of CRISPR to genetically alter two fetuses grown through IVF. Although this was ostensibly to provide genetic resilience against HIV infections, imagine what would happen if we started tinkering with neural circuitry and intelligence.”
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Posted in Human Robots
#434235 The Milestones of Human Progress We ...
When you look back at 2018, do you see a good or a bad year? Chances are, your perception of the year involves fixating on all the global and personal challenges it brought. In fact, every year, we tend to look back at the previous year as “one of the most difficult” and hope that the following year is more exciting and fruitful.
But in the grander context of human history, 2018 was an extraordinarily positive year. In fact, every year has been getting progressively better.
Before we dive into some of the highlights of human progress from 2018, let’s make one thing clear. There is no doubt that there are many overwhelming global challenges facing our species. From climate change to growing wealth inequality, we are far from living in a utopia.
Yet it’s important to recognize that both our news outlets and audiences have been disproportionately fixated on negative news. This emphasis on bad news is detrimental to our sense of empowerment as a species.
So let’s take a break from all the disproportionate negativity and have a look back on how humanity pushed boundaries in 2018.
On Track to Becoming an Interplanetary Species
We often forget how far we’ve come since the very first humans left the African savanna, populated the entire planet, and developed powerful technological capabilities. Our desire to explore the unknown has shaped the course of human evolution and will continue to do so.
This year, we continued to push the boundaries of space exploration. As depicted in the enchanting short film Wanderers, humanity’s destiny is the stars. We are born to be wanderers of the cosmos and the everlasting unknown.
SpaceX had 21 successful launches in 2018 and closed the year with a successful GPS launch. The latest test flight by Virgin Galactic was also an incredible milestone, as SpaceShipTwo was welcomed into space. Richard Branson and his team expect that space tourism will be a reality within the next 18 months.
Our understanding of the cosmos is also moving forward with continuous breakthroughs in astrophysics and astronomy. One notable example is the MARS InSight Mission, which uses cutting-edge instruments to study Mars’ interior structure and has even given us the first recordings of sound on Mars.
Understanding and Tackling Disease
Thanks to advancements in science and medicine, we are currently living longer, healthier, and wealthier lives than at any other point in human history. In fact, for most of human history, life expectancy at birth was around 30. Today it is more than 70 worldwide, and in the developed parts of the world, more than 80.
Brilliant researchers around the world are pushing for even better health outcomes. This year, we saw promising treatments emerge against Alzheimers disease, rheumatoid arthritis, multiple scleroris, and even the flu.
The deadliest disease of them all, cancer, is also being tackled. According to the American Association of Cancer Research, 22 revolutionary treatments for cancer were approved in the last year, and the death rate in adults is also in decline. Advancements in immunotherapy, genetic engineering, stem cells, and nanotechnology are all powerful resources to tackle killer diseases.
Breakthrough Mental Health Therapy
While cleaner energy, access to education, and higher employment rates can improve quality of life, they do not guarantee happiness and inner peace. According to the World Economic Forum, mental health disorders affect one in four people globally, and in many places they are significantly under-reported. More people are beginning to realize that our mental health is just as important as our physical health, and that we ought to take care of our minds just as much as our bodies.
We are seeing the rise of applications that put mental well-being at their center. Breakthrough advancements in genetics are allowing us to better understand the genetic makeup of disorders like clinical depression or Schizophrenia, and paving the way for personalized medical treatment. We are also seeing the rise of increasingly effective therapeutic treatments for anxiety.
This year saw many milestones for a whole new revolutionary area in mental health: psychedelic therapy. Earlier this summer, the FDA granted breakthrough therapy designation to MDMA for the treatment of PTSD, after several phases of successful trails. Similar research has discovered that Psilocybin (also known as magic mushrooms) combined with therapy is far more effective than traditional forms of treatment for depression and anxiety.
Moral and Social Progress
Innovation is often associated with economic and technological progress. However, we also need leaps of progress in our morality, values, and policies. Throughout the 21st century, we’ve made massive strides in rights for women and children, civil rights, LGBT rights, animal rights, and beyond. However, with rising nationalism and xenophobia in many parts of the developed world, there is significant work to be done on this front.
All hope is not lost, as we saw many noteworthy milestones this year. In January 2018, Iceland introduced the equal wage law, bringing an end to the gender wage gap. On September 6th, the Indian Supreme Court decriminalized homosexuality, marking a historical moment. Earlier in December, the European Commission released a draft of ethics guidelines for trustworthy artificial intelligence. Such are just a few examples of positive progress in social justice, ethics, and policy.
We are also seeing a global rise in social impact entrepreneurship. Emerging startups are no longer valued simply based on their profits and revenue, but also on the level of positive impact they are having on the world at large. The world’s leading innovators are not asking themselves “How can I become rich?” but rather “How can I solve this global challenge?”
Intelligently Optimistic for 2019
It’s becoming more and more clear that we are living in the most exciting time in human history. Even more, we mustn’t be afraid to be optimistic about 2019.
An optimistic mindset can be grounded in rationality and evidence. Intelligent optimism is all about being excited about the future in an informed and rational way. The mindset is critical if we are to get everyone excited about the future by highlighting the rapid progress we have made and recognizing the tremendous potential humans have to find solutions to our problems.
In his latest TED talk, Steven Pinker points out, “Progress does not mean that everything becomes better for everyone everywhere all the time. That would be a miracle, and progress is not a miracle but problem-solving. Problems are inevitable and solutions create new problems which have to be solved in their turn.”
Let us not forget that in cosmic time scales, our entire species’ lifetime, including all of human history, is the equivalent of the blink of an eye. The probability of us existing both as an intelligent species and as individuals is so astoundingly low that it’s practically non-existent. We are the products of 14 billion years of cosmic evolution and extraordinarily good fortune. Let’s recognize and leverage this wondrous opportunity, and pave an exciting way forward.
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Posted in Human Robots