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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?
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The key difference between science fiction and fantasy is that science fiction is entirely possible because of its grounding in scientific facts, while fantasy is not. This is where Black Mirror is both an entertaining and terrifying work of science fiction. Created by Charlie Brooker, the anthological series tells cautionary tales of emerging technology that could one day be an integral part of our everyday lives.
While watching the often alarming episodes, one can’t help but recognize the eerie similarities to some of the tech tools that are already abundant in our lives today. In fact, many previous Black Mirror predictions are already becoming reality.
The latest season of Black Mirror was arguably darker than ever. This time, Brooker seemed to focus on the ethical implications of one particular area: neurotechnology.
Warning: The remainder of this article may contain spoilers from Season 4 of Black Mirror.
Most of the storylines from season four revolve around neurotechnology and brain-machine interfaces. They are based in a world where people have the power to upload their consciousness onto machines, have fully immersive experiences in virtual reality, merge their minds with other minds, record others’ memories, and even track what others are thinking, feeling, and doing.
How can all this ever be possible? Well, these capabilities are already being developed by pioneers and researchers globally. Early last year, Elon Musk unveiled Neuralink, a company whose goal is to merge the human mind with AI through a neural lace. We’ve already connected two brains via the internet, allowing one brain to communicate with another. Various research teams have been able to develop mechanisms for “reading minds” or reconstructing memories of individuals via devices. The list goes on.
With many of the technologies we see in Black Mirror it’s not a question of if, but when. Futurist Ray Kurzweil has predicted that by the 2030s we will be able to upload our consciousness onto the cloud via nanobots that will “provide full-immersion virtual reality from within the nervous system, provide direct brain-to-brain communication over the internet, and otherwise greatly expand human intelligence.” While other experts continue to challenge Kurzweil on the exact year we’ll accomplish this feat, with the current exponential growth of our technological capabilities, we’re on track to get there eventually.
As always, technology is only half the conversation. Equally fascinating are the many ethical and moral questions this topic raises.
For instance, with the increasing convergence of artificial intelligence and virtual reality, we have to ask ourselves if our morality from the physical world transfers equally into the virtual world. The first episode of season four, USS Calister, tells the story of a VR pioneer, Robert Daley, who creates breakthrough AI and VR to satisfy his personal frustrations and sexual urges. He uses the DNA of his coworkers (and their children) to re-create them digitally in his virtual world, to which he escapes to torture them, while they continue to be indifferent in the “real” world.
Audiences are left asking themselves: should what happens in the digital world be considered any less “real” than the physical world? How do we know if the individuals in the virtual world (who are ultimately based on algorithms) have true feelings or sentiments? Have they been developed to exhibit characteristics associated with suffering, or can they really feel suffering? Fascinatingly, these questions point to the hard problem of consciousness—the question of if, why, and how a given physical process generates the specific experience it does—which remains a major mystery in neuroscience.
Towards the end of USS Calister, the hostages of Daley’s virtual world attempt to escape through suicide, by committing an act that will delete the code that allows them to exist. This raises yet another mind-boggling ethical question: if we “delete” code that signifies a digital being, should that be considered murder (or suicide, in this case)? Why shouldn’t it? When we murder someone we are, in essence, taking away their capacity to live and to be, without their consent. By unplugging a self-aware AI, wouldn’t we be violating its basic right to live in the same why? Does AI, as code, even have rights?
Brain implants can also have a radical impact on our self-identity and how we define the word “I”. In the episode Black Museum, instead of witnessing just one horror, we get a series of scares in little segments. One of those segments tells the story of a father who attempts to reincarnate the mother of his child by uploading her consciousness into his mind and allowing her to live in his head (essentially giving him multiple personality disorder). In this way, she can experience special moments with their son.
With “no privacy for him, and no agency for her” the good intention slowly goes very wrong. This story raises a critical question: should we be allowed to upload consciousness into limited bodies? Even more, if we are to upload our minds into “the cloud,” at what point do we lose our individuality to become one collective being?
These questions can form the basis of hours of debate, but we’re just getting started. There are no right or wrong answers with many of these moral dilemmas, but we need to start having such discussions.
The Downside of Dystopian Sci-Fi
Like last season’s San Junipero, one episode of the series, Hang the DJ, had an uplifting ending. Yet the overwhelming majority of the stories in Black Mirror continue to focus on the darkest side of human nature, feeding into the pre-existing paranoia of the general public. There is certainly some value in this; it’s important to be aware of the dangers of technology. After all, what better way to explore these dangers before they occur than through speculative fiction?
A big takeaway from every tale told in the series is that the greatest threat to humanity does not come from technology, but from ourselves. Technology itself is not inherently good or evil; it all comes down to how we choose to use it as a society. So for those of you who are techno-paranoid, beware, for it’s not the technology you should fear, but the humans who get their hands on it.
While we can paint negative visions for the future, though, it is also important to paint positive ones. The kind of visions we set for ourselves have the power to inspire and motivate generations. Many people are inherently pessimistic when thinking about the future, and that pessimism in turn can shape their contributions to humanity.
While utopia may not exist, the future of our species could and should be one of solving global challenges, abundance, prosperity, liberation, and cosmic transcendence. Now that would be a thrilling episode to watch.
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Technological progress has radically transformed our concept of privacy. How we share information and display our identities has changed as we’ve migrated to the digital world.
As the Guardian states, “We now carry with us everywhere devices that give us access to all the world’s information, but they can also offer almost all the world vast quantities of information about us.” We are all leaving digital footprints as we navigate through the internet. While sometimes this information can be harmless, it’s often valuable to various stakeholders, including governments, corporations, marketers, and criminals.
The ethical debate around privacy is complex. The reality is that our definition and standards for privacy have evolved over time, and will continue to do so in the next few decades.
Implications of Emerging Technologies
Protecting privacy will only become more challenging as we experience the emergence of technologies such as virtual reality, the Internet of Things, brain-machine interfaces, and much more.
Virtual reality headsets are already gathering information about users’ locations and physical movements. In the future all of our emotional experiences, reactions, and interactions in the virtual world will be able to be accessed and analyzed. As virtual reality becomes more immersive and indistinguishable from physical reality, technology companies will be able to gather an unprecedented amount of data.
It doesn’t end there. The Internet of Things will be able to gather live data from our homes, cities and institutions. Drones may be able to spy on us as we live our everyday lives. As the amount of genetic data gathered increases, the privacy of our genes, too, may be compromised.
It gets even more concerning when we look farther into the future. As companies like Neuralink attempt to merge the human brain with machines, we are left with powerful implications for privacy. Brain-machine interfaces by nature operate by extracting information from the brain and manipulating it in order to accomplish goals. There are many parties that can benefit and take advantage of the information from the interface.
Marketing companies, for instance, would take an interest in better understanding how consumers think and consequently have their thoughts modified. Employers could use the information to find new ways to improve productivity or even monitor their employees. There will notably be risks of “brain hacking,” which we must take extreme precaution against. However, it is important to note that lesser versions of these risks currently exist, i.e., by phone hacking, identify fraud, and the like.
A New Much-Needed Definition of Privacy
In many ways we are already cyborgs interfacing with technology. According to theories like the extended mind hypothesis, our technological devices are an extension of our identities. We use our phones to store memories, retrieve information, and communicate. We use powerful tools like the Hubble Telescope to extend our sense of sight. In parallel, one can argue that the digital world has become an extension of the physical world.
These technological tools are a part of who we are. This has led to many ethical and societal implications. Our Facebook profiles can be processed to infer secondary information about us, such as sexual orientation, political and religious views, race, substance use, intelligence, and personality. Some argue that many of our devices may be mapping our every move. Your browsing history could be spied on and even sold in the open market.
While the argument to protect privacy and individuals’ information is valid to a certain extent, we may also have to accept the possibility that privacy will become obsolete in the future. We have inherently become more open as a society in the digital world, voluntarily sharing our identities, interests, views, and personalities.
“The question we are left with is, at what point does the tradeoff between transparency and privacy become detrimental?”
There also seems to be a contradiction with the positive trend towards mass transparency and the need to protect privacy. Many advocate for a massive decentralization and openness of information through mechanisms like blockchain.
The question we are left with is, at what point does the tradeoff between transparency and privacy become detrimental? We want to live in a world of fewer secrets, but also don’t want to live in a world where our every move is followed (not to mention our every feeling, thought and interaction). So, how do we find a balance?
Traditionally, privacy is used synonymously with secrecy. Many are led to believe that if you keep your personal information secret, then you’ve accomplished privacy. Danny Weitzner, director of the MIT Internet Policy Research Initiative, rejects this notion and argues that this old definition of privacy is dead.
From Witzner’s perspective, protecting privacy in the digital age means creating rules that require governments and businesses to be transparent about how they use our information. In other terms, we can’t bring the business of data to an end, but we can do a better job of controlling it. If these stakeholders spy on our personal information, then we should have the right to spy on how they spy on us.
The Role of Policy and Discourse
Almost always, policy has been too slow to adapt to the societal and ethical implications of technological progress. And sometimes the wrong laws can do more harm than good. For instance, in March, the US House of Representatives voted to allow internet service providers to sell your web browsing history on the open market.
More often than not, the bureaucratic nature of governance can’t keep up with exponential growth. New technologies are emerging every day and transforming society. Can we confidently claim that our world leaders, politicians, and local representatives are having these conversations and debates? Are they putting a focus on the ethical and societal implications of emerging technologies? Probably not.
We also can’t underestimate the role of public awareness and digital activism. There needs to be an emphasis on educating and engaging the general public about the complexities of these issues and the potential solutions available. The current solution may not be robust or clear, but having these discussions will get us there.
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