Tag Archives: following
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.
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 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.
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?
Abundance Digital is my online educational portal and community of abundance-minded entrepreneurs. You’ll find weekly video updates from Peter, a curated newsfeed of exponential news, and a place to share your bold ideas. Click here to learn more and sign up.
Image Credit: ktsdesign / Shutterstock.com Continue reading
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.”
Image Credit: hywards / Shutterstock.com Continue reading