Tag Archives: discovery
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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Superconductors are among the most bizarre and exciting materials yet discovered. Counterintuitive quantum-mechanical effects mean that, below a critical temperature, they have zero electrical resistance. This property alone is more than enough to spark the imagination.
A current that could flow forever without losing any energy means transmission of power with virtually no losses in the cables. When renewable energy sources start to dominate the grid and high-voltage transmission across continents becomes important to overcome intermittency, lossless cables will result in substantial savings.
What’s more, a superconducting wire carrying a current that never, ever diminishes would act as a perfect store of electrical energy. Unlike batteries, which degrade over time, if the resistance is truly zero, you could return to the superconductor in a billion years and find that same old current flowing through it. Energy could be captured and stored indefinitely!
With no resistance, a huge current could be passed through the superconducting wire and, in turn, produce magnetic fields of incredible power.
You could use them to levitate trains and produce astonishing accelerations, thereby revolutionizing the transport system. You could use them in power plants—replacing conventional methods which spin turbines in magnetic fields to generate electricity—and in quantum computers as the two-level system required for a “qubit,” in which the zeros and ones are replaced by current flowing clockwise or counterclockwise in a superconductor.
Arthur C. Clarke famously said that any sufficiently advanced technology is indistinguishable from magic; superconductors can certainly seem like magical devices. So, why aren’t they busy remaking the world? There’s a problem—that critical temperature.
For all known materials, it’s hundreds of degrees below freezing. Superconductors also have a critical magnetic field; beyond a certain magnetic field strength, they cease to work. There’s a tradeoff: materials with an intrinsically high critical temperature can also often provide the largest magnetic fields when cooled well below that temperature.
This has meant that superconductor applications so far have been limited to situations where you can afford to cool the components of your system to close to absolute zero: in particle accelerators and experimental nuclear fusion reactors, for example.
But even as some aspects of superconductor technology become mature in limited applications, the search for higher temperature superconductors moves on. Many physicists still believe a room-temperature superconductor could exist. Such a discovery would unleash amazing new technologies.
The Quest for Room-Temperature Superconductors
After Heike Kamerlingh Onnes discovered superconductivity by accident while attempting to prove Lord Kelvin’s theory that resistance would increase with decreasing temperature, theorists scrambled to explain the new property in the hope that understanding it might allow for room-temperature superconductors to be synthesized.
They came up with the BCS theory, which explained some of the properties of superconductors. It also predicted that the dream of technologists, a room-temperature superconductor, could not exist; the maximum temperature for superconductivity according to BCS theory was just 30 K.
Then, in the 1980s, the field changed again with the discovery of unconventional, or high-temperature, superconductivity. “High temperature” is still very cold: the highest temperature for superconductivity achieved was -70°C for hydrogen sulphide at extremely high pressures. For normal pressures, -140°C is near the upper limit. Unfortunately, high-temperature superconductors—which require relatively cheap liquid nitrogen, rather than liquid helium, to cool—are mostly brittle ceramics, which are expensive to form into wires and have limited application.
Given the limitations of high-temperature superconductors, researchers continue to believe there’s a better option awaiting discovery—an incredible new material that checks boxes like superconductivity approaching room temperature, affordability, and practicality.
Without a detailed theoretical understanding of how this phenomenon occurs—although incremental progress happens all the time—scientists can occasionally feel like they’re taking educated guesses at materials that might be likely candidates. It’s a little like trying to guess a phone number, but with the periodic table of elements instead of digits.
Yet the prospect remains, in the words of one researcher, tantalizing. A Nobel Prize and potentially changing the world of energy and electricity is not bad for a day’s work.
Some research focuses on cuprates, complex crystals that contain layers of copper and oxygen atoms. Doping cuprates with various different elements, such exotic compounds as mercury barium calcium copper oxide, are amongst the best superconductors known today.
Research also continues into some anomalous but unexplained reports that graphite soaked in water can act as a room-temperature superconductor, but there’s no indication that this could be used for technological applications yet.
In early 2017, as part of the ongoing effort to explore the most extreme and exotic forms of matter we can create on Earth, researchers managed to compress hydrogen into a metal.
The pressure required to do this was more than that at the core of the Earth and thousands of times higher than that at the bottom of the ocean. Some researchers in the field, called condensed-matter physics, doubt that metallic hydrogen was produced at all.
It’s considered possible that metallic hydrogen could be a room-temperature superconductor. But getting the samples to stick around long enough for detailed testing has proved tricky, with the diamonds containing the metallic hydrogen suffering a “catastrophic failure” under the pressure.
Superconductivity—or behavior that strongly resembles it—was also observed in yttrium barium copper oxide (YBCO) at room temperature in 2014. The only catch was that this electron transport lasted for a tiny fraction of a second and required the material to be bombarded with pulsed lasers.
Not very practical, you might say, but tantalizing nonetheless.
Other new materials display enticing properties too. The 2016 Nobel Prize in Physics was awarded for the theoretical work that characterizes topological insulators—materials that exhibit similarly strange quantum behaviors. They can be considered perfect insulators for the bulk of the material but extraordinarily good conductors in a thin layer on the surface.
Microsoft is betting on topological insulators as the key component in their attempt at a quantum computer. They’ve also been considered potentially important components in miniaturized circuitry.
A number of remarkable electronic transport properties have also been observed in new, “2D” structures—like graphene, these are materials synthesized to be as thick as a single atom or molecule. And research continues into how we can utilize the superconductors we’ve already discovered; for example, some teams are trying to develop insulating material that prevents superconducting HVDC cable from overheating.
Room-temperature superconductivity remains as elusive and exciting as it has been for over a century. It is unclear whether a room-temperature superconductor can exist, but the discovery of high-temperature superconductors is a promising indicator that unconventional and highly useful quantum effects may be discovered in completely unexpected materials.
Perhaps in the future—through artificial intelligence simulations or the serendipitous discoveries of a 21st century Kamerlingh Onnes—this little piece of magic could move into the realm of reality.
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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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