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#439077 How Scientists Grew Human Muscles in Pig ...
The little pigs bouncing around the lab looked exceedingly normal. Yet their adorable exterior hid a remarkable secret: each piglet carried two different sets of genes. For now, both sets came from their own species. But one day, one of those sets may be human.
The piglets are chimeras—creatures with intermingled sets of genes, as if multiple entities were seamlessly mashed together. Named after the Greek lion-goat-serpent monsters, chimeras may hold the key to an endless supply of human organs and tissues for transplant. The crux is growing these human parts in another animal—one close enough in size and function to our own.
Last week, a team from the University of Minnesota unveiled two mind-bending chimeras. One was joyous little piglets, each propelled by muscles grown from a different pig. Another was pig embryos, transplanted into surrogate pigs, that developed human muscles for more than 20 days.
The study, led by Drs. Mary and Daniel Garry at the University of Minnesota, had a therapeutic point: engineering a brilliant way to replace muscle loss, especially for the muscles around our skeletons that allow us to move and navigate the world. Trauma and injury, such as from firearm wounds or car crashes, can damage muscle tissue beyond the point of repair. Unfortunately, muscles are also stubborn in that donor tissue from cadavers doesn’t usually “take” at the injury site. For now, there are no effective treatments for severe muscle death, called volumetric muscle loss.
The new human-pig hybrids are designed to tackle this problem. Muscle wasting aside, the study also points to a clever “hack” that increases the amount of human tissue inside a growing pig embryo.
If further improved, the technology could “provide an unlimited supply of organs for transplantation,” said Dr. Mary Garry to Inverse. What’s more, because the human tissue can be sourced from patients themselves, the risk of rejection by the immune system is relatively low—even when grown inside a pig.
“The shortage of organs for heart transplantation, vascular grafting, and skeletal muscle is staggering,” said Garry. Human-animal chimeras could have a “seismic impact” that transforms organ transplantation and helps solve the organ shortage crisis.
That is, if society accepts the idea of a semi-humanoid pig.
Wait…But How?
The new study took a page from previous chimera recipes.
The main ingredients and steps go like this: first, you need an embryo that lacks the ability to develop a tissue or organ. This leaves an “empty slot” of sorts that you can fill with another set of genes—pig, human, or even monkey.
Second, you need to fine-tune the recipe so that the embryos “take” the new genes, incorporating them into their bodies as if they were their own. Third, the new genes activate to instruct the growing embryo to make the necessary tissue or organs without harming the overall animal. Finally, the foreign genes need to stay put, without cells migrating to another body part—say, the brain.
Not exactly straightforward, eh? The piglets are technological wonders that mix cutting-edge gene editing with cloning technologies.
The team went for two chimeras: one with two sets of pig genes, the other with a pig and human mix. Both started with a pig embryo that can’t make its own skeletal muscles (those are the muscles surrounding your bones). Using CRISPR, the gene-editing Swiss Army Knife, they snipped out three genes that are absolutely necessary for those muscles to develop. Like hitting a bullseye with three arrows simultaneously, it’s already a technological feat.
Here’s the really clever part: the muscles around your bones have a slightly different genetic makeup than the ones that line your blood vessels or the ones that pump your heart. While the resulting pig embryos had severe muscle deformities as they developed, their hearts beat as normal. This means the gene editing cut only impacted skeletal muscles.
Then came step two: replacing the missing genes. Using a microneedle, the team injected a fertilized and slightly developed pig egg—called a blastomere—into the embryo. If left on its natural course, a blastomere eventually develops into another embryo. This step “smashes” the two sets of genes together, with the newcomer filling the muscle void. The hybrid embryo was then placed into a surrogate, and roughly four months later, chimeric piglets were born.
Equipped with foreign DNA, the little guys nevertheless seemed totally normal, nosing around the lab and running everywhere without obvious clumsy stumbles. Under the microscope, their “xenomorph” muscles were indistinguishable from run-of-the-mill average muscle tissue—no signs of damage or inflammation, and as stretchy and tough as muscles usually are. What’s more, the foreign DNA seemed to have only developed into muscles, even though they were prevalent across the body. Extensive fishing experiments found no trace of the injected set of genes inside blood vessels or the brain.
A Better Human-Pig Hybrid
Confident in their recipe, the team next repeated the experiment with human cells, with a twist. Instead of using controversial human embryonic stem cells, which are obtained from aborted fetuses, they relied on induced pluripotent stem cells (iPSCs). These are skin cells that have been reverted back into a stem cell state.
Unlike previous attempts at making human chimeras, the team then scoured the genetic landscape of how pig and human embryos develop to find any genetic “brakes” that could derail the process. One gene, TP53, stood out, which was then promptly eliminated with CRISPR.
This approach provides a way for future studies to similarly increase the efficiency of interspecies chimeras, the team said.
The human-pig embryos were then carefully grown inside surrogate pigs for less than a month, and extensively analyzed. By day 20, the hybrids had already grown detectable human skeletal muscle. Similar to the pig-pig chimeras, the team didn’t detect any signs that the human genes had sprouted cells that would eventually become neurons or other non-muscle cells.
For now, human-animal chimeras are not allowed to grow to term, in part to stem the theoretical possibility of engineering humanoid hybrid animals (shudder). However, a sentient human-pig chimera is something that the team specifically addressed. Through multiple experiments, they found no trace of human genes in the embryos’ brain stem cells 20 and 27 days into development. Similarly, human donor genes were absent in cells that would become the hybrid embryos’ reproductive cells.
Despite bioethical quandaries and legal restrictions, human-animal chimeras have taken off, both as a source of insight into human brain development and a well of personalized organs and tissues for transplant. In 2019, Japan lifted its ban on developing human brain cells inside animal embryos, as well as the term limit—to global controversy. There’s also the question of animal welfare, given that hybrid clones will essentially become involuntary organ donors.
As the debates rage on, scientists are nevertheless pushing the limits of human-animal chimeras, while treading as carefully as possible.
“Our data…support the feasibility of the generation of these interspecies chimeras, which will serve as a model for translational research or, one day, as a source for xenotransplantation,” the team said.
Image Credit: Christopher Carson on Unsplash Continue reading
Posted in Human Robots
#439023 In ‘Klara and the Sun,’ We Glimpse ...
In a store in the center of an unnamed city, humanoid robots are displayed alongside housewares and magazines. They watch the fast-moving world outside the window, anxiously awaiting the arrival of customers who might buy them and take them home. Among them is Klara, a particularly astute robot who loves the sun and wants to learn as much as possible about humans and the world they live in.
So begins Kazuo Ishiguro’s new novel Klara and the Sun, published earlier this month. The book, told from Klara’s perspective, portrays an eerie future society in which intelligent machines and other advanced technologies have been integrated into daily life, but not everyone is happy about it.
Technological unemployment, the progress of artificial intelligence, inequality, the safety and ethics of gene editing, increasing loneliness and isolation—all of which we’re grappling with today—show up in Ishiguro’s world. It’s like he hit a fast-forward button, mirroring back to us how things might play out if we don’t approach these technologies with caution and foresight.
The wealthy genetically edit or “lift” their children to set them up for success, while the poor have to make do with the regular old brains and bodies bequeathed them by evolution. Lifted and unlifted kids generally don’t mix, and this is just one of many sinister delineations between a new breed of haves and have-nots.
There’s anger about robots’ steady infiltration into everyday life, and questions about how similar their rights should be to those of humans. “First they take the jobs. Then they take the seats at the theater?” one woman fumes.
References to “changes” and “substitutions” allude to an economy where automation has eliminated millions of jobs. While “post-employed” people squat in abandoned buildings and fringe communities arm themselves in preparation for conflict, those whose livelihoods haven’t been destroyed can afford to have live-in housekeepers and buy Artificial Friends (or AFs) for their lonely children.
“The old traditional model that we still live with now—where most of us can get some kind of paid work in exchange for our services or the goods we make—has broken down,” Ishiguro said in a podcast discussion of the novel. “We’re not talking just about the difference between rich and poor getting bigger. We’re talking about a gap appearing between people who participate in society in an obvious way and people who do not.”
He has a point; as much as techno-optimists claim that the economic changes brought by automation and AI will give us all more free time, let us work less, and devote time to our passion projects, how would that actually play out? What would millions of “post-employed” people receiving basic income actually do with their time and energy?
In the novel, we don’t get much of a glimpse of this side of the equation, but we do see how the wealthy live. After a long wait, just as the store manager seems ready to give up on selling her, Klara is chosen by a 14-year-old girl named Josie, the daughter of a woman who wears “high-rank clothes” and lives in a large, sunny home outside the city. Cheerful and kind, Josie suffers from an unspecified illness that periodically flares up and leaves her confined to her bed for days at a time.
Her life seems somewhat bleak, the need for an AF clear. In this future world, the children of the wealthy no longer go to school together, instead studying alone at home on their digital devices. “Interaction meetings” are set up for them to learn to socialize, their parents carefully eavesdropping from the next room and trying not to intervene when there’s conflict or hurt feelings.
Klara does her best to be a friend, aide, and confidante to Josie while continuing to learn about the world around her and decode the mysteries of human behavior. We surmise that she was programmed with a basic ability to understand emotions, which evolves along with her other types of intelligence. “I believe I have many feelings. The more I observe, the more feelings become available to me,” she explains to one character.
Ishiguro does an excellent job of representing Klara’s mind: a blend of pre-determined programming, observation, and continuous learning. Her narration has qualities both robotic and human; we can tell when something has been programmed in—she “Gives Privacy” to the humans around her when that’s appropriate, for example—and when she’s figured something out for herself.
But the author maintains some mystery around Klara’s inner emotional life. “Does she actually understand human emotions, or is she just observing human emotions and simulating them within herself?” he said. “I suppose the question comes back to, what are our emotions as human beings? What do they amount to?”
Klara is particularly attuned to human loneliness, since she essentially was made to help prevent it. It is, in her view, peoples’ biggest fear, and something they’ll go to great lengths to avoid, yet can never fully escape. “Perhaps all humans are lonely,” she says.
Warding off loneliness through technology isn’t a futuristic idea, it’s something we’ve been doing for a long time, with the technologies at hand growing more and more sophisticated. Products like AFs already exist. There’s XiaoIce, a chatbot that uses “sentiment analysis” to keep its 660 million users engaged, and Azuma Hikari, a character-based AI designed to “bring comfort” to users whose lives lack emotional connection with other humans.
The mere existence of these tools would be sinister if it wasn’t for their widespread adoption; when millions of people use AIs to fill a void in their lives, it raises deeper questions about our ability to connect with each other and whether technology is building it up or tearing it down.
This isn’t the only big question the novel tackles. An overarching theme is one we’ve been increasingly contemplating as computers start to acquire more complex capabilities, like the beginnings of creativity or emotional awareness: What is it that truly makes us human?
“Do you believe in the human heart?” one character asks. “I don’t mean simply the organ, obviously. I’m speaking in the poetic sense. The human heart. Do you think there is such a thing? Something that makes each of us special and individual?”
The alternative, at least in the story, is that people don’t have a unique essence, but rather we’re all a blend of traits and personalities that can be reduced to strings of code. Our understanding of the brain is still elementary, but at some level, doesn’t all human experience boil down to the firing of billions of neurons between our ears? Will we one day—in a future beyond that painted by Ishiguro, but certainly foreshadowed by it—be able to “decode” our humanity to the point that there’s nothing mysterious left about it? “A human heart is bound to be complex,” Klara says. “But it must be limited.”
Whether or not you agree, Klara and the Sun is worth the read. It’s both a marvelous, engaging story about what it means to love and be human, and a prescient warning to approach technological change with caution and nuance. We’re already living in a world where AI keeps us company, influences our behavior, and is wreaking various forms of havoc. Ishiguro’s novel is a snapshot of one of our possible futures, told through the eyes of a robot who keeps you rooting for her to the end.
Image Credit: Marion Wellmann from Pixabay Continue reading
Posted in Human Robots
#437209 A Renaissance of Genomics and Drugs Is ...
The causes of aging are extremely complex and unclear. But with longevity clinical trials increasing, more answers—and questions—are emerging than ever before.
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 turn those answers into practical ways to extend our healthspan.
In this article, I’ll explore how genome sequencing and editing, along with new classes of anti-aging drugs, are augmenting our biology to further extend our healthy lives.
Genome Sequencing and 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 for 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 $1,500 in 2015.
Today, the cost of genome sequencing has dropped below $600, 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 article).
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 have used CRISPR to genetically engineer cocaine resistance into mice, reverse the gene defect causing Duchenne muscular dystrophy (DMD) in dogs, and reduce genetic deafness in mice.
Already this year, CRISPR-edited immune cells have been shown to successfully kill cancer cells in human patients. Researchers have discovered ways to activate CRISPR with light and use the gene-editing technology to better understand Alzheimer’s disease progression.
With great power comes great responsibility, and the opportunity for 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. Because Jiankui forged ethical review documents and misled doctors in the process, he was sentenced to three years in prison and fined $429,000 last December.
Coupled with significant ethical conversations necessary for progress, 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, and 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 Biotechnologies is pioneering a programmable gene therapy that can destroy cells based on their internal biochemistry.
SIWA Therapeutics is 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.
(1) 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 for 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 went public in 2018) 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, and a 30.6 percent decrease in respiratory tract infection.
Impressive, to say the least.
(2) 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.
(3) 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 first 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 article 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 toward 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?
Join Me
(1) A360 Executive Mastermind: If you’re an exponentially and abundance-minded entrepreneur who would like coaching directly from me, consider joining my Abundance 360 Mastermind, a highly selective community of 360 CEOs and entrepreneurs who I coach for 3 days every January in Beverly Hills, Ca. Through A360, I provide my members with context and clarity about how converging exponential technologies will transform every industry. I’m committed to running A360 for the course of an ongoing 25-year journey as a “countdown to the Singularity.”
If you’d like to learn more and consider joining our 2021 membership, apply here.
(2) Abundance-Digital Online Community: I’ve also created a Digital/Online community of bold, abundance-minded entrepreneurs called Abundance-Digital. Abundance-Digital is Singularity University’s ‘onramp’ for exponential entrepreneurs—those who want to get involved and play at a higher level. Click here to learn more.
(Both A360 and Abundance-Digital are part of Singularity University—your participation opens you to a global community.)
This article originally appeared on diamandis.com. Read the original article here.
Image Credit: Arek Socha from Pixabay Continue reading
Posted in Human Robots