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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
#434270 AI Will Create Millions More Jobs Than ...
In the past few years, artificial intelligence has advanced so quickly that it now seems hardly a month goes by without a newsworthy AI breakthrough. In areas as wide-ranging as speech translation, medical diagnosis, and gameplay, we have seen computers outperform humans in startling ways.
This has sparked a discussion about how AI will impact employment. Some fear that as AI improves, it will supplant workers, creating an ever-growing pool of unemployable humans who cannot compete economically with machines.
This concern, while understandable, is unfounded. In fact, AI will be the greatest job engine the world has ever seen.
New Technology Isn’t a New Phenomenon
On the one hand, those who predict massive job loss from AI can be excused. It is easier to see existing jobs disrupted by new technology than to envision what new jobs the technology will enable.
But on the other hand, radical technological advances aren’t a new phenomenon. Technology has progressed nonstop for 250 years, and in the US unemployment has stayed between 5 to 10 percent for almost all that time, even when radical new technologies like steam power and electricity came on the scene.
But you don’t have to look back to steam, or even electricity. Just look at the internet. Go back 25 years, well within the memory of today’s pessimistic prognosticators, to 1993. The web browser Mosaic had just been released, and the phrase “surfing the web,” that most mixed of metaphors, was just a few months old.
If someone had asked you what would be the result of connecting a couple billion computers into a giant network with common protocols, you might have predicted that email would cause us to mail fewer letters, and the web might cause us to read fewer newspapers and perhaps even do our shopping online. If you were particularly farsighted, you might have speculated that travel agents and stockbrokers would be adversely affected by this technology. And based on those surmises, you might have thought the internet would destroy jobs.
But now we know what really happened. The obvious changes did occur. But a slew of unexpected changes happened as well. We got thousands of new companies worth trillions of dollars. We bettered the lot of virtually everyone on the planet touched by the technology. Dozens of new careers emerged, from web designer to data scientist to online marketer. The cost of starting a business with worldwide reach plummeted, and the cost of communicating with customers and leads went to nearly zero. Vast storehouses of information were made freely available and used by entrepreneurs around the globe to build new kinds of businesses.
But yes, we mail fewer letters and buy fewer newspapers.
The Rise of Artificial Intelligence
Then along came a new, even bigger technology: artificial intelligence. You hear the same refrain: “It will destroy jobs.”
Consider the ATM. If you had to point to a technology that looked as though it would replace people, the ATM might look like a good bet; it is, after all, an automated teller machine. And yet, there are more tellers now than when ATMs were widely released. How can this be? Simple: ATMs lowered the cost of opening bank branches, and banks responded by opening more, which required hiring more tellers.
In this manner, AI will create millions of jobs that are far beyond our ability to imagine. For instance, AI is becoming adept at language translation—and according to the US Bureau of Labor Statistics, demand for human translators is skyrocketing. Why? If the cost of basic translation drops to nearly zero, the cost of doing business with those who speak other languages falls. Thus, it emboldens companies to do more business overseas, creating more work for human translators. AI may do the simple translations, but humans are needed for the nuanced kind.
In fact, the BLS forecasts faster-than-average job growth in many occupations that AI is expected to impact: accountants, forensic scientists, geological technicians, technical writers, MRI operators, dietitians, financial specialists, web developers, loan officers, medical secretaries, and customer service representatives, to name a very few. These fields will not experience job growth in spite of AI, but through it.
But just as with the internet, the real gains in jobs will come from places where our imaginations cannot yet take us.
Parsing Pessimism
You may recall waking up one morning to the news that “47 percent of jobs will be lost to technology.”
That report by Carl Frey and Michael Osborne is a fine piece of work, but readers and the media distorted their 47 percent number. What the authors actually said is that some functions within 47 percent of jobs will be automated, not that 47 percent of jobs will disappear.
Frey and Osborne go on to rank occupations by “probability of computerization” and give the following jobs a 65 percent or higher probability: social science research assistants, atmospheric and space scientists, and pharmacy aides. So what does this mean? Social science professors will no longer have research assistants? Of course they will. They will just do different things because much of what they do today will be automated.
The intergovernmental Organization for Economic Co-operation and Development released a report of their own in 2016. This report, titled “The Risk of Automation for Jobs in OECD Countries,” applies a different “whole occupations” methodology and puts the share of jobs potentially lost to computerization at nine percent. That is normal churn for the economy.
But what of the skills gap? Will AI eliminate low-skilled workers and create high-skilled job opportunities? The relevant question is whether most people can do a job that’s just a little more complicated than the one they currently have. This is exactly what happened with the industrial revolution; farmers became factory workers, factory workers became factory managers, and so on.
Embracing AI in the Workplace
A January 2018 Accenture report titled “Reworking the Revolution” estimates that new applications of AI combined with human collaboration could boost employment worldwide as much as 10 percent by 2020.
Electricity changed the world, as did mechanical power, as did the assembly line. No one can reasonably claim that we would be better off without those technologies. Each of them bettered our lives, created jobs, and raised wages. AI will be bigger than electricity, bigger than mechanization, bigger than anything that has come before it.
This is how free economies work, and why we have never run out of jobs due to automation. There are not a fixed number of jobs that automation steals one by one, resulting in progressively more unemployment. There are as many jobs in the world as there are buyers and sellers of labor.
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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
#433884 Designer Babies, and Their Babies: How ...
As if stand-alone technologies weren’t advancing fast enough, we’re in age where we must study the intersection points of these technologies. How is what’s happening in robotics influenced by what’s happening in 3D printing? What could be made possible by applying the latest advances in quantum computing to nanotechnology?
Along these lines, one crucial tech intersection is that of artificial intelligence and genomics. Each field is seeing constant progress, but Jamie Metzl believes it’s their convergence that will really push us into uncharted territory, beyond even what we’ve imagined in science fiction. “There’s going to be this push and pull, this competition between the reality of our biology with its built-in limitations and the scope of our aspirations,” he said.
Metzl is a senior fellow at the Atlantic Council and author of the upcoming book Hacking Darwin: Genetic Engineering and the Future of Humanity. At Singularity University’s Exponential Medicine conference last week, he shared his insights on genomics and AI, and where their convergence could take us.
Life As We Know It
Metzl explained how genomics as a field evolved slowly—and then quickly. In 1953, James Watson and Francis Crick identified the double helix structure of DNA, and realized that the order of the base pairs held a treasure trove of genetic information. There was such a thing as a book of life, and we’d found it.
In 2003, when the Human Genome Project was completed (after 13 years and $2.7 billion), we learned the order of the genome’s 3 billion base pairs, and the location of specific genes on our chromosomes. Not only did a book of life exist, we figured out how to read it.
Jamie Metzl at Exponential Medicine
Fifteen years after that, it’s 2018 and precision gene editing in plants, animals, and humans is changing everything, and quickly pushing us into an entirely new frontier. Forget reading the book of life—we’re now learning how to write it.
“Readable, writable, and hackable, what’s clear is that human beings are recognizing that we are another form of information technology, and just like our IT has entered this exponential curve of discovery, we will have that with ourselves,” Metzl said. “And it’s intersecting with the AI revolution.”
Learning About Life Meets Machine Learning
In 2016, DeepMind’s AlphaGo program outsmarted the world’s top Go player. In 2017 AlphaGo Zero was created: unlike AlphaGo, AlphaGo Zero wasn’t trained using previous human games of Go, but was simply given the rules of Go—and in four days it defeated the AlphaGo program.
Our own biology is, of course, vastly more complex than the game of Go, and that, Metzl said, is our starting point. “The system of our own biology that we are trying to understand is massively, but very importantly not infinitely, complex,” he added.
Getting a standardized set of rules for our biology—and, eventually, maybe even outsmarting our biology—will require genomic data. Lots of it.
Multiple countries already starting to produce this data. The UK’s National Health Service recently announced a plan to sequence the genomes of five million Britons over the next five years. In the US the All of Us Research Program will sequence a million Americans. China is the most aggressive in sequencing its population, with a goal of sequencing half of all newborns by 2020.
“We’re going to get these massive pools of sequenced genomic data,” Metzl said. “The real gold will come from comparing people’s sequenced genomes to their electronic health records, and ultimately their life records.” Getting people comfortable with allowing open access to their data will be another matter; Metzl mentioned that Luna DNA and others have strategies to help people get comfortable with giving consent to their private information. But this is where China’s lack of privacy protection could end up being a significant advantage.
To compare genotypes and phenotypes at scale—first millions, then hundreds of millions, then eventually billions, Metzl said—we’re going to need AI and big data analytic tools, and algorithms far beyond what we have now. These tools will let us move from precision medicine to predictive medicine, knowing precisely when and where different diseases are going to occur and shutting them down before they start.
But, Metzl said, “As we unlock the genetics of ourselves, it’s not going to be about just healthcare. It’s ultimately going to be about who and what we are as humans. It’s going to be about identity.”
Designer Babies, and Their Babies
In Metzl’s mind, the most serious application of our genomic knowledge will be in embryo selection.
Currently, in-vitro fertilization (IVF) procedures can extract around 15 eggs, fertilize them, then do pre-implantation genetic testing; right now what’s knowable is single-gene mutation diseases and simple traits like hair color and eye color. As we get to the millions and then billions of people with sequences, we’ll have information about how these genetics work, and we’re going to be able to make much more informed choices,” Metzl said.
Imagine going to a fertility clinic in 2023. You give a skin graft or a blood sample, and using in-vitro gametogenesis (IVG)—infertility be damned—your skin or blood cells are induced to become eggs or sperm, which are then combined to create embryos. The dozens or hundreds of embryos created from artificial gametes each have a few cells extracted from them, and these cells are sequenced. The sequences will tell you the likelihood of specific traits and disease states were that embryo to be implanted and taken to full term. “With really anything that has a genetic foundation, we’ll be able to predict with increasing levels of accuracy how that potential child will be realized as a human being,” Metzl said.
This, he added, could lead to some wild and frightening possibilities: if you have 1,000 eggs and you pick one based on its optimal genetic sequence, you could then mate your embryo with somebody else who has done the same thing in a different genetic line. “Your five-day-old embryo and their five-day-old embryo could have a child using the same IVG process,” Metzl said. “Then that child could have a child with another five-day-old embryo from another genetic line, and you could go on and on down the line.”
Sounds insane, right? But wait, there’s more: as Jason Pontin reported earlier this year in Wired, “Gene-editing technologies such as Crispr-Cas9 would make it relatively easy to repair, add, or remove genes during the IVG process, eliminating diseases or conferring advantages that would ripple through a child’s genome. This all may sound like science fiction, but to those following the research, the combination of IVG and gene editing appears highly likely, if not inevitable.”
From Crazy to Commonplace?
It’s a slippery slope from gene editing and embryo-mating to a dystopian race to build the most perfect humans possible. If somebody’s investing so much time and energy in selecting their embryo, Metzl asked, how will they think about the mating choices of their children? IVG could quickly leave the realm of healthcare and enter that of evolution.
“We all need to be part of an inclusive, integrated, global dialogue on the future of our species,” Metzl said. “Healthcare professionals are essential nodes in this.” Not least among this dialogue should be the question of access to tech like IVG; are there steps we can take to keep it from becoming a tool for a wealthy minority, and thereby perpetuating inequality and further polarizing societies?
As Pontin points out, at its inception 40 years ago IVF also sparked fear, confusion, and resistance—and now it’s as normal and common as could be, with millions of healthy babies conceived using the technology.
The disruption that genomics, AI, and IVG will bring to reproduction could follow a similar story cycle—if we’re smart about it. As Metzl put it, “This must be regulated, because it is life.”
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Posted in Human Robots