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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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Big data, personalized medicine, artificial intelligence. String these three buzzphrases together, and what do you have?
A system that may revolutionize the future of healthcare, by bringing sophisticated health data directly to patients for them to ponder, digest, and act upon—and potentially stop diseases in their tracks.
At Singularity University’s Exponential Medicine conference in San Diego this week, Dr. Ran Balicer, director of the Clalit Research Institute in Israel, painted a futuristic picture of how big data can merge with personalized healthcare into an app-based system in which the patient is in control.
Dr. Ran Balicer at Exponential Medicine
Picture this: instead of going to a physician with your ailments, your doctor calls you with some bad news: “Within six hours, you’re going to have a heart attack. So why don’t you come into the clinic and we can fix that.” Crisis averted.
Following the treatment, you’re at home monitoring your biomarkers, lab test results, and other health information through an app with a clean, beautiful user interface. Within the app, you can observe how various health-influencing life habits—smoking, drinking, insufficient sleep—influence your chance of future cardiovascular disease risks by toggling their levels up or down.
There’s more: you can also set a health goal within the app—for example, stop smoking—which automatically informs your physician. The app will then suggest pharmaceuticals to help you ditch the nicotine and automatically sends the prescription to your local drug store. You’ll also immediately find a list of nearby support groups that can help you reach your health goal.
With this hefty dose of AI, you’re in charge of your health—in fact, probably more so than under current healthcare systems.
Sound fantastical? In fact, this type of preemptive care is already being provided in some countries, including Israel, at a massive scale, said Balicer. By mining datasets with deep learning and other powerful AI tools, we can predict the future—and put it into the hands of patients.
The Israeli Advantage
In order to apply big data approaches to medicine, you first need a giant database.
Israel is ahead of the game in this regard. With decades of electronic health records aggregated within a central warehouse, Israel offers a wealth of health-related data on the scale of millions of people and billions of data points. The data is incredibly multiplex, covering lab tests, drugs, hospital admissions, medical procedures, and more.
One of Balicer’s early successes was an algorithm that predicts diabetes, which allowed the team to notify physicians to target their care. Clalit has also been busy digging into data that predicts winter pneumonia, osteoporosis, and a long list of other preventable diseases.
So far, Balicer’s predictive health system has only been tested on a pilot group of patients, but he is expecting to roll out the platform to all patients in the database in the next few months.
Truly Personalized Medicine
To Balicer, whatever a machine can do better, it should be welcomed to do. AI diagnosticians have already enjoyed plenty of successes—but their collaboration remains mostly with physicians, at a point in time when the patient is already ill.
A particularly powerful use of AI in medicine is to bring insights and trends directly to the patient, such that they can take control over their own health and medical care.
For example, take the problem of tailored drug dosing. Current drug doses are based on average results conducted during clinical trials—the dosing is not tailored for any specific patient’s genetic and health makeup. But what if a doctor had already seen millions of other patients similar to your case, and could generate dosing recommendations more relevant to you based on that particular group of patients?
Such personalized recommendations are beyond the ability of any single human doctor. But with the help of AI, which can quickly process massive datasets to find similarities, doctors may soon be able to prescribe individually-tailored medications.
Tailored treatment doesn’t stop there. Another issue with pharmaceuticals and treatment regimes is that they often come with side effects: potentially health-threatening reactions that may, or may not, happen to you based on your biometrics.
Back in 2017, the New England Journal of Medicine launched the SPRINT Data Analysis Challenge, which urged physicians and data analysts to identify novel clinical findings using shared clinical trial data.
Working with Dr. Noa Dagan at the Clalit Research Institute, Balicer and team developed an algorithm that recommends whether or not a patient receives a particularly intensive treatment regime for hypertension.
Rather than simply looking at one outcome—normalized blood pressure—the algorithm takes into account an individual’s specific characteristics, laying out the treatment’s predicted benefits and harms for a particular patient.
“We built thousands of models for each patient to comprehensively understand the impact of the treatment for the individual; for example, a reduced risk for stroke and cardiovascular-related deaths could be accompanied by an increase in serious renal failure,” said Balicer. “This approach allows a truly personalized balance—allowing patients and their physicians to ultimately decide if the risks of the treatment are worth the benefits.”
This is already personalized medicine at its finest. But Balicer didn’t stop there.
We are not the sum of our biologics and medical stats, he said. A truly personalized approach needs to take a patient’s needs and goals and the sacrifices and tradeoffs they’re willing to make into account, rather than having the physician make decisions for them.
Balicer’s preventative system adds this layer of complexity by giving weights to different outcomes based on patients’ input of their own health goals. Rather than blindly following big data, the system holistically integrates the patient’s opinion to make recommendations.
Balicer’s system is just one example of how AI can truly transform personalized health care. The next big challenge is to work with physicians to further optimize these systems, in a way that doctors can easily integrate them into their workflow and embrace the technology.
“Health systems will not be replaced by algorithms, rest assured,” concluded Balicer, “but health systems that don’t use algorithms will be replaced by those that do.”
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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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Pedro Domingos on the Arms Race in Artificial Intelligence
Christoph Scheuermann and Bernhard Zand | Spiegel Online
“AI lowers the cost of knowledge by orders of magnitude. One good, effective machine learning system can do the work of a million people, whether it’s for commercial purposes or for cyberespionage. Imagine a country that produces a thousand times more knowledge than another. This is the challenge we are facing.”
Gene Therapy Could Free Some People From a Lifetime of Blood Transfusions
Emily Mullin | MIT Technology Review
“A one-time, experimental treatment for an inherited blood disorder has shown dramatic results in a small study. …[Lead author Alexis Thompson] says the effect on patients has been remarkable. ‘They have been tied to this ongoing medical therapy that is burdensome and expensive for their whole lives,’ she says. ‘Gene therapy has allowed people to have aspirations and really pursue them.’ ”
The Revolutionary Giant Ocean Cleanup Machine Is About to Set Sail
Adele Peters | Fast Company
“By the end of 2018, the nonprofit says it will bring back its first harvest of ocean plastic from the North Pacific Gyre, along with concrete proof that the design works. The organization expects to bring 5,000 kilograms of plastic ashore per month with its first system. With a full fleet of systems deployed, it believes that it can collect half of the plastic trash in the Great Pacific Garbage Patch—around 40,000 metric tons—within five years.”
Autonomous Boats Will Be on the Market Sooner Than Self-Driving Cars
Tracey Lindeman | Motherboard
“Some unmanned watercraft…may be at sea commercially before 2020. That’s partly because automating all ships could generate a ridiculous amount of revenue. According to the United Nations, 90 percent of the world’s trade is carried by sea and 10.3 billion tons of products were shipped in 2016.”
Style Is an Algorithm
Kyle Chayka | Racked
“Confronting the Echo Look’s opaque statements on my fashion sense, I realize that all of these algorithmic experiences are matters of taste: the question of what we like and why we like it, and what it means that taste is increasingly dictated by black-box robots like the camera on my shelf.”
How Apple Will Use AR to Reinvent the Human-Computer Interface
Tim Bajarin | Fast Company
“It’s in Apple’s DNA to continually deliver the ‘next’ major advancement to the personal computing experience. Its innovation in man-machine interfaces started with the Mac and then extended to the iPod, the iPhone, the iPad, and most recently, the Apple Watch. Now, get ready for the next chapter, as Apple tackles augmented reality, in a way that could fundamentally transform the human-computer interface.”
Advanced Microscope Shows Cells at Work in Incredible Detail
Steve Dent | Engadget
“For the first time, scientists have peered into living cells and created videos showing how they function with unprecedented 3D detail. Using a special microscope and new lighting techniques, a team from Harvard and the Howard Hughes Medical Institute captured zebrafish immune cell interactions with unheard-of 3D detail and resolution.”
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