Tag Archives: gene
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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From a first-principles perspective, the task of feeding eight billion people boils down to converting energy from the sun into chemical energy in our bodies.
Traditionally, solar energy is converted by photosynthesis into carbohydrates in plants (i.e., biomass), which are either eaten by the vegans amongst us, or fed to animals, for those with a carnivorous preference.
Today, the process of feeding humanity is extremely inefficient.
If we could radically reinvent what we eat, and how we create that food, what might you imagine that “future of food” would look like?
In this post we’ll cover:
CRISPR engineered foods
The alt-protein revolution
Let’s dive in.
Where we grow our food…
The average American meal travels over 1,500 miles from farm to table. Wine from France, beef from Texas, potatoes from Idaho.
Imagine instead growing all of your food in a 50-story tall vertical farm in downtown LA or off-shore on the Great Lakes where the travel distance is no longer 1,500 miles but 50 miles.
Delocalized farming will minimize travel costs at the same time that it maximizes freshness.
Perhaps more importantly, vertical farming also allows tomorrow’s farmer the ability to control the exact conditions of her plants year round.
Rather than allowing the vagaries of the weather and soil conditions to dictate crop quality and yield, we can now perfectly control the growing cycle.
LED lighting provides the crops with the maximum amount of light, at the perfect frequency, 24 hours a day, 7 days a week.
At the same time, sensors and robots provide the root system the exact pH and micronutrients required, while fine-tuning the temperature of the farm.
Such precision farming can generate yields that are 200% to 400% above normal.
Next let’s explore how we can precision-engineer the genetic properties of the plant itself.
CRISPR and Genetically Engineered Foods
What food do we grow?
A fundamental shift is occurring in our relationship with agriculture. We are going from evolution by natural selection (Darwinism) to evolution by human direction.
CRISPR (the cutting edge gene editing tool) is providing a pathway for plant breeding that is more predictable, faster and less expensive than traditional breeding methods.
Rather than our crops being subject to nature’s random, environmental whim, CRISPR unlocks our capability to modify our crops to match the available environment.
Further, using CRISPR we will be able to optimize the nutrient density of our crops, enhancing their value and volume.
CRISPR may also hold the key to eliminating common allergens from crops. As we identify the allergen gene in peanuts, for instance, we can use CRISPR to silence that gene, making the crops we raise safer for and more accessible to a rapidly growing population.
Yet another application is our ability to make plants resistant to infection or more resistant to drought or cold.
Helping to accelerate the impact of CRISPR, the USDA recently announced that genetically engineered crops will not be regulated—providing an opening for entrepreneurs to capitalize on the opportunities for optimization CRISPR enables.
CRISPR applications in agriculture are an opportunity to help a billion people and become a billionaire in the process.
Protecting crops against volatile environments, combating crop diseases and increasing nutrient values, CRISPR is a promising tool to help feed the world’s rising population.
The Alt-Protein/Lab-Grown Meat Revolution
Something like a third of the Earth’s arable land is used for raising livestock—a massive amount of land—and global demand for meat is predicted to double in the coming decade.
Today, we must grow an entire cow—all bones, skin, and internals included—to produce a steak.
Imagine if we could instead start with a single muscle stem cell and only grow the steak, without needing the rest of the cow? Think of it as cellular agriculture.
Imagine returning millions, perhaps billions, of acres of grazing land back to the wilderness? This is the promise of lab-grown meats.
Lab-grown meat can also be engineered (using technology like CRISPR) to be packed with nutrients and be the healthiest, most delicious protein possible.
We’re watching this technology develop in real time. Several startups across the globe are already working to bring artificial meats to the food industry.
JUST, Inc. (previously Hampton Creek) run by my friend Josh Tetrick, has been on a mission to build a food system where everyone can get and afford delicious, nutritious food. They started by exploring 300,000+ species of plants all around the world to see how they can make food better and now are investing heavily in stem-cell-grown meats.
Backed by Richard Branson and Bill Gates, Memphis Meats is working on ways to produce real meat from animal cells, rather than whole animals. So far, they have produced beef, chicken, and duck using cultured cells from living animals.
As with vertical farming, transitioning production of our majority protein source to a carefully cultivated environment allows for agriculture to optimize inputs (water, soil, energy, land footprint), nutrients and, importantly, taste.
Vertical farming and cellular agriculture are reinventing how we think about our food supply chain and what food we produce.
The next question to answer is who will be producing the food?
Let’s look back at how farming evolved through history.
Farmers 0.0 (Neolithic Revolution, around 9000 BCE): The hunter-gatherer to agriculture transition gains momentum, and humans cultivated the ability to domesticate plants for food production.
Farmers 1.0 (until around the 19th century): Farmers spent all day in the field performing backbreaking labor, and agriculture accounted for most jobs.
Farmers 2.0 (mid-20th century, Green Revolution): From the invention of the first farm tractor in 1812 through today, transformative mechanical biochemical technologies (fertilizer) boosted yields and made the job of farming easier, driving the US farm job rate down to less than two percent today.
Farmers 3.0: In the near future, farmers will leverage exponential technologies (e.g., AI, networks, sensors, robotics, drones), CRISPR and genetic engineering, and new business models to solve the world’s greatest food challenges and efficiently feed the eight-billion-plus people on Earth.
An important driver of the Farmer 3.0 evolution is the delocalization of agriculture driven by vertical and urban farms. Vertical farms and urban agriculture are empowering a new breed of agriculture entrepreneurs.
Let’s take a look at an innovative incubator in Brooklyn, New York called Square Roots.
Ten farm-in-a-shipping-containers in a Brooklyn parking lot represent the first Square Roots campus. Each 8-foot x 8.5-foot x 20-foot shipping container contains an equivalent of 2 acres of produce and can yield more than 50 pounds of produce each week.
For 13 months, one cohort of next-generation food entrepreneurs takes part in a curriculum with foundations in farming, business, community and leadership.
The urban farming incubator raised a $5.4 million seed funding round in August 2017.
Training a new breed of entrepreneurs to apply exponential technology to growing food is essential to the future of farming.
One of our massive transformative purposes at the Abundance Group is to empower entrepreneurs to generate extraordinary wealth while creating a world of abundance. Vertical farms and cellular agriculture are key elements enabling the next generation of food and agriculture entrepreneurs.
Technology is driving food abundance.
We’re already seeing food become demonetized, as the graph below shows.
From 1960 to 2014, the percent of income spent on food in the U.S. fell from 19 percent to under 10 percent of total disposable income—a dramatic decrease over the 40 percent of household income spent on food in 1900.
The dropping percent of per-capita disposable income spent on food. Source: USDA, Economic Research Service, Food Expenditure Series
Ultimately, technology has enabled a massive variety of food at a significantly reduced cost and with fewer resources used for production.
We’re increasingly going to optimize and fortify the food supply chain to achieve more reliable, predictable, and nutritious ways to obtain basic sustenance.
And that means a world with abundant, nutritious, and inexpensive food for every man, woman, and child.
What an extraordinary time to be alive.
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Once upon a time, a powerful Sumerian king named Gilgamesh went on a quest, as such characters often do in these stories of myth and legend. Gilgamesh had witnessed the death of his best friend, Enkidu, and, fearing a similar fate, went in search of immortality. The great king failed to find the secret of eternal life but took solace that his deeds would live well beyond his mortal years.
Fast-forward four thousand years, give or take a century, and Gilgamesh (as famous as any B-list celebrity today, despite the passage of time) would probably be heartened to learn that many others have taken up his search for longevity. Today, though, instead of battling epic monsters and the machinations of fickle gods, those seeking to enhance and extend life are cutting-edge scientists and visionary entrepreneurs who are helping unlock the secrets of human biology.
Chief among them is Aubrey de Grey, a biomedical gerontologist who founded the SENS Research Foundation, a Silicon Valley-based research organization that seeks to advance the application of regenerative medicine to age-related diseases. SENS stands for Strategies for Engineered Negligible Senescence, a term coined by de Grey to describe a broad array (seven, to be precise) of medical interventions that attempt to repair or prevent different types of molecular and cellular damage that eventually lead to age-related diseases like cancer and Alzheimer’s.
Many of the strategies focus on senescent cells, which accumulate in tissues and organs as people age. Not quite dead, senescent cells stop dividing but are still metabolically active, spewing out all sorts of proteins and other molecules that can cause inflammation and other problems. In a young body, that’s usually not a problem (and probably part of general biological maintenance), as a healthy immune system can go to work to put out most fires.
However, as we age, senescent cells continue to accumulate, and at some point the immune system retires from fire watch. Welcome to old age.
Of Mice and Men
Researchers like de Grey believe that treating the cellular underpinnings of aging could not only prevent disease but significantly extend human lifespans. How long? Well, if you’re talking to de Grey, Biblical proportions—on the order of centuries.
De Grey says that science has made great strides toward that end in the last 15 years, such as the ability to copy mitochondrial DNA to the nucleus. Mitochondria serve as the power plant of the cell but are highly susceptible to mutations that lead to cellular degeneration. Copying the mitochondrial DNA into the nucleus would help protect it from damage.
Another achievement occurred about six years ago when scientists first figured out how to kill senescent cells. That discovery led to a spate of new experiments in mice indicating that removing these ticking-time-bomb cells prevented disease and even extended their lifespans. Now the anti-aging therapy is about to be tested in humans.
“As for the next few years, I think the stream of advances is likely to become a flood—once the first steps are made, things get progressively easier and faster,” de Grey tells Singularity Hub. “I think there’s a good chance that we will achieve really dramatic rejuvenation of mice within only six to eight years: maybe taking middle-aged mice and doubling their remaining lifespan, which is an order of magnitude more than can be done today.”
Not Horsing Around
Richard G.A. Faragher, a professor of biogerontology at the University of Brighton in the United Kingdom, recently made discoveries in the lab regarding the rejuvenation of senescent cells with chemical compounds found in foods like chocolate and red wine. He hopes to apply his findings to an animal model in the future—in this case,horses.
“We have been very fortunate in receiving some funding from an animal welfare charity to look at potential treatments for older horses,” he explains to Singularity Hub in an email. “I think this is a great idea. Many aspects of the physiology we are studying are common between horses and humans.”
What Faragher and his colleagues demonstrated in a paper published in BMC Cell Biology last year was that resveralogues, chemicals based on resveratrol, were able to reactivate a protein called a splicing factor that is involved in gene regulation. Within hours, the chemicals caused the cells to rejuvenate and start dividing like younger cells.
“If treatments work in our old pony systems, then I am sure they could be translated into clinical trials in humans,” Faragher says. “How long is purely a matter of money. Given suitable funding, I would hope to see a trial within five years.”
Show Them the Money
Faragher argues that the recent breakthroughs aren’t because a result of emerging technologies like artificial intelligence or the gene-editing tool CRISPR, but a paradigm shift in how scientists understand the underpinnings of cellular aging. Solving the “aging problem” isn’t a question of technology but of money, he says.
“Frankly, when AI and CRISPR have removed cystic fibrosis, Duchenne muscular dystrophy or Gaucher syndrome, I’ll be much more willing to hear tales of amazing progress. Go fix a single, highly penetrant genetic disease in the population using this flashy stuff and then we’ll talk,” he says. “My faith resides in the most potent technological development of all: money.”
De Grey is less flippant about the role that technology will play in the quest to defeat aging. AI, CRISPR, protein engineering, advances in stem cell therapies, and immune system engineering—all will have a part.
“There is not really anything distinctive about the ways in which these technologies will contribute,” he says. “What’s distinctive is that we will need all of these technologies, because there are so many different types of damage to repair and they each require different tricks.”
It’s in the Blood
A startup in the San Francisco Bay Area believes machines can play a big role in discovering the right combination of factors that lead to longer and healthier lives—and then develop drugs that exploit those findings.
BioAge Labs raised nearly $11 million last year for its machine learning platform that crunches big data sets to find blood factors, such as proteins or metabolites, that are tied to a person’s underlying biological age. The startup claims that these factors can predict how long a person will live.
“Our interest in this comes out of research into parabiosis, where joining the circulatory systems of old and young mice—so that they share the same blood—has been demonstrated to make old mice healthier and more robust,” Dr. Eric Morgen, chief medical officer at BioAge, tells Singularity Hub.
Based on that idea, he explains, it should be possible to alter those good or bad factors to produce a rejuvenating effect.
“Our main focus at BioAge is to identify these types of factors in our human cohort data, characterize the important molecular pathways they are involved in, and then drug those pathways,” he says. “This is a really hard problem, and we use machine learning to mine these complex datasets to determine which individual factors and molecular pathways best reflect biological age.”
Saving for the Future
Of course, there’s no telling when any of these anti-aging therapies will come to market. That’s why Forever Labs, a biotechnology startup out of Ann Arbor, Michigan, wants your stem cells now. The company offers a service to cryogenically freeze stem cells taken from bone marrow.
The theory behind the procedure, according to Forever Labs CEO Steven Clausnitzer, is based on research showing that stem cells may be a key component for repairing cellular damage. That’s because stem cells can develop into many different cell types and can divide endlessly to replenish other cells. Clausnitzer notes that there are upwards of a thousand clinical studies looking at using stem cells to treat age-related conditions such as cardiovascular disease.
However, stem cells come with their own expiration date, which usually coincides with the age that most people start experiencing serious health problems. Stem cells harvested from bone marrow at a younger age can potentially provide a therapeutic resource in the future.
“We believe strongly that by having access to your own best possible selves, you’re going to be well positioned to lead healthier, longer lives,” he tells Singularity Hub.
“There’s a compelling argument to be made that if you started to maintain the bone marrow population, the amount of nuclear cells in your bone marrow, and to re-up them so that they aren’t declining with age, it stands to reason that you could absolutely mitigate things like cardiovascular disease and stroke and Alzheimer’s,” he adds.
Clausnitzer notes that the stored stem cells can be used today in developing therapies to treat chronic conditions such as osteoarthritis. However, the more exciting prospect—and the reason he put his own 38-year-old stem cells on ice—is that he believes future stem cell therapies can help stave off the ravages of age-related disease.
“I can start reintroducing them not to treat age-related disease but to treat the decline in the stem-cell niche itself, so that I don’t ever get an age-related disease,” he says. “I don’t think that it equates to immortality, but it certainly is a step in that direction.”
Indecisive on Immortality
The societal implications of a longer-living human species are a guessing game at this point. We do know that by mid-century, the global population of those aged 65 and older will reach 1.6 billion, while those older than 80 will hit nearly 450 million, according to the National Academies of Science. If many of those people could enjoy healthy lives in their twilight years, an enormous medical cost could be avoided.
Faragher is certainly working toward a future where human health is ubiquitous. Human immortality is another question entirely.
“The longer lifespans become, the more heavily we may need to control birth rates and thus we may have fewer new minds. This could have a heavy ‘opportunity cost’ in terms of progress,” he says.
And does anyone truly want to live forever?
“There have been happy moments in my life but I have also suffered some traumatic disappointments. No [drug] will wash those experiences out of me,” Faragher says. “I no longer view my future with unqualified enthusiasm, and I do not think I am the only middle-aged man to feel that way. I don’t think it is an accident that so many ‘immortalists’ are young.
“They should be careful what they wish for.”
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