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#438779 Meet Catfish Charlie, the CIA’s ...
Photo: CIA Museum
CIA roboticists designed Catfish Charlie to take water samples undetected. Why they wanted a spy fish for such a purpose remains classified.
In 1961, Tom Rogers of the Leo Burnett Agency created Charlie the Tuna, a jive-talking cartoon mascot and spokesfish for the StarKist brand. The popular ad campaign ran for several decades, and its catchphrase “Sorry, Charlie” quickly hooked itself in the American lexicon.
When the CIA’s Office of Advanced Technologies and Programs started conducting some fish-focused research in the 1990s, Charlie must have seemed like the perfect code name. Except that the CIA’s Charlie was a catfish. And it was a robot.
More precisely, Charlie was an unmanned underwater vehicle (UUV) designed to surreptitiously collect water samples. Its handler controlled the fish via a line-of-sight radio handset. Not much has been revealed about the fish’s construction except that its body contained a pressure hull, ballast system, and communications system, while its tail housed the propulsion. At 61 centimeters long, Charlie wouldn’t set any biggest-fish records. (Some species of catfish can grow to 2 meters.) Whether Charlie reeled in any useful intel is unknown, as details of its missions are still classified.
For exploring watery environments, nothing beats a robot
The CIA was far from alone in its pursuit of UUVs nor was it the first agency to do so. In the United States, such research began in earnest in the 1950s, with the U.S. Navy’s funding of technology for deep-sea rescue and salvage operations. Other projects looked at sea drones for surveillance and scientific data collection.
Aaron Marburg, a principal electrical and computer engineer who works on UUVs at the University of Washington’s Applied Physics Laboratory, notes that the world’s oceans are largely off-limits to crewed vessels. “The nature of the oceans is that we can only go there with robots,” he told me in a recent Zoom call. To explore those uncharted regions, he said, “we are forced to solve the technical problems and make the robots work.”
Image: Thomas Wells/Applied Physics Laboratory/University of Washington
An oil painting commemorates SPURV, a series of underwater research robots built by the University of Washington’s Applied Physics Lab. In nearly 400 deployments, no SPURVs were lost.
One of the earliest UUVs happens to sit in the hall outside Marburg’s office: the Self-Propelled Underwater Research Vehicle, or SPURV, developed at the applied physics lab beginning in the late ’50s. SPURV’s original purpose was to gather data on the physical properties of the sea, in particular temperature and sound velocity. Unlike Charlie, with its fishy exterior, SPURV had a utilitarian torpedo shape that was more in line with its mission. Just over 3 meters long, it could dive to 3,600 meters, had a top speed of 2.5 m/s, and operated for 5.5 hours on a battery pack. Data was recorded to magnetic tape and later transferred to a photosensitive paper strip recorder or other computer-compatible media and then plotted using an IBM 1130.
Over time, SPURV’s instrumentation grew more capable, and the scope of the project expanded. In one study, for example, SPURV carried a fluorometer to measure the dispersion of dye in the water, to support wake studies. The project was so successful that additional SPURVs were developed, eventually completing nearly 400 missions by the time it ended in 1979.
Working on underwater robots, Marburg says, means balancing technical risks and mission objectives against constraints on funding and other resources. Support for purely speculative research in this area is rare. The goal, then, is to build UUVs that are simple, effective, and reliable. “No one wants to write a report to their funders saying, ‘Sorry, the batteries died, and we lost our million-dollar robot fish in a current,’ ” Marburg says.
A robot fish called SoFi
Since SPURV, there have been many other unmanned underwater vehicles, of various shapes and sizes and for various missions, developed in the United States and elsewhere. UUVs and their autonomous cousins, AUVs, are now routinely used for scientific research, education, and surveillance.
At least a few of these robots have been fish-inspired. In the mid-1990s, for instance, engineers at MIT worked on a RoboTuna, also nicknamed Charlie. Modeled loosely on a blue-fin tuna, it had a propulsion system that mimicked the tail fin of a real fish. This was a big departure from the screws or propellers used on UUVs like SPURV. But this Charlie never swam on its own; it was always tethered to a bank of instruments. The MIT group’s next effort, a RoboPike called Wanda, overcame this limitation and swam freely, but never learned to avoid running into the sides of its tank.
Fast-forward 25 years, and a team from MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) unveiled SoFi, a decidedly more fishy robot designed to swim next to real fish without disturbing them. Controlled by a retrofitted Super Nintendo handset, SoFi could dive more than 15 meters, control its own buoyancy, and swim around for up to 40 minutes between battery charges. Noting that SoFi’s creators tested their robot fish in the gorgeous waters off Fiji, IEEE Spectrum’s Evan Ackerman noted, “Part of me is convinced that roboticists take on projects like these…because it’s a great way to justify a trip somewhere exotic.”
SoFi, Wanda, and both Charlies are all examples of biomimetics, a term coined in 1974 to describe the study of biological mechanisms, processes, structures, and substances. Biomimetics looks to nature to inspire design.
Sometimes, the resulting technology proves to be more efficient than its natural counterpart, as Richard James Clapham discovered while researching robotic fish for his Ph.D. at the University of Essex, in England. Under the supervision of robotics expert Huosheng Hu, Clapham studied the swimming motion of Cyprinus carpio, the common carp. He then developed four robots that incorporated carplike swimming, the most capable of which was iSplash-II. When tested under ideal conditions—that is, a tank 5 meters long, 2 meters wide, and 1.5 meters deep—iSpash-II obtained a maximum velocity of 11.6 body lengths per second (or about 3.7 m/s). That’s faster than a real carp, which averages a top velocity of 10 body lengths per second. But iSplash-II fell short of the peak performance of a fish darting quickly to avoid a predator.
Of course, swimming in a test pool or placid lake is one thing; surviving the rough and tumble of a breaking wave is another matter. The latter is something that roboticist Kathryn Daltorio has explored in depth.
Daltorio, an assistant professor at Case Western Reserve University and codirector of the Center for Biologically Inspired Robotics Research there, has studied the movements of cockroaches, earthworms, and crabs for clues on how to build better robots. After watching a crab navigate from the sandy beach to shallow water without being thrown off course by a wave, she was inspired to create an amphibious robot with tapered, curved feet that could dig into the sand. This design allowed her robot to withstand forces up to 138 percent of its body weight.
Photo: Nicole Graf
This robotic crab created by Case Western’s Kathryn Daltorio imitates how real crabs grab the sand to avoid being toppled by waves.
In her designs, Daltorio is following architect Louis Sullivan’s famous maxim: Form follows function. She isn’t trying to imitate the aesthetics of nature—her robot bears only a passing resemblance to a crab—but rather the best functionality. She looks at how animals interact with their environments and steals evolution’s best ideas.
And yet, Daltorio admits, there is also a place for realistic-looking robotic fish, because they can capture the imagination and spark interest in robotics as well as nature. And unlike a hyperrealistic humanoid, a robotic fish is unlikely to fall into the creepiness of the uncanny valley.
In writing this column, I was delighted to come across plenty of recent examples of such robotic fish. Ryomei Engineering, a subsidiary of Mitsubishi Heavy Industries, has developed several: a robo-coelacanth, a robotic gold koi, and a robotic carp. The coelacanth was designed as an educational tool for aquariums, to present a lifelike specimen of a rarely seen fish that is often only known by its fossil record. Meanwhile, engineers at the University of Kitakyushu in Japan created Tai-robot-kun, a credible-looking sea bream. And a team at Evologics, based in Berlin, came up with the BOSS manta ray.
Whatever their official purpose, these nature-inspired robocreatures can inspire us in return. UUVs that open up new and wondrous vistas on the world’s oceans can extend humankind’s ability to explore. We create them, and they enhance us, and that strikes me as a very fair and worthy exchange.
This article appears in the March 2021 print issue as “Catfish, Robot, Swimmer, Spy.”
About the Author
Allison Marsh is an associate professor of history at the University of South Carolina and codirector of the university’s Ann Johnson Institute for Science, Technology & Society. Continue reading
Posted in Human Robots
#437261 How AI Will Make Drug Discovery ...
If you had to guess how long it takes for a drug to go from an idea to your pharmacy, what would you guess? Three years? Five years? How about the cost? $30 million? $100 million?
Well, here’s the sobering truth: 90 percent of all drug possibilities fail. The few that do succeed take an average of 10 years to reach the market and cost anywhere from $2.5 billion to $12 billion to get there.
But what if we could generate novel molecules to target any disease, overnight, ready for clinical trials? Imagine leveraging machine learning to accomplish with 50 people what the pharmaceutical industry can barely do with an army of 5,000.
Welcome to the future of AI and low-cost, ultra-fast, and personalized drug discovery. Let’s dive in.
GANs & Drugs
Around 2012, computer scientist-turned-biophysicist Alex Zhavoronkov started to notice that artificial intelligence was getting increasingly good at image, voice, and text recognition. He knew that all three tasks shared a critical commonality. In each, massive datasets were available, making it easy to train up an AI.
But similar datasets were present in pharmacology. So, back in 2014, Zhavoronkov started wondering if he could use these datasets and AI to significantly speed up the drug discovery process. He’d heard about a new technique in artificial intelligence known as generative adversarial networks (or GANs). By pitting two neural nets against one another (adversarial), the system can start with minimal instructions and produce novel outcomes (generative). At the time, researchers had been using GANs to do things like design new objects or create one-of-a-kind, fake human faces, but Zhavoronkov wanted to apply them to pharmacology.
He figured GANs would allow researchers to verbally describe drug attributes: “The compound should inhibit protein X at concentration Y with minimal side effects in humans,” and then the AI could construct the molecule from scratch. To turn his idea into reality, Zhavoronkov set up Insilico Medicine on the campus of Johns Hopkins University in Baltimore, Maryland, and rolled up his sleeves.
Instead of beginning their process in some exotic locale, Insilico’s “drug discovery engine” sifts millions of data samples to determine the signature biological characteristics of specific diseases. The engine then identifies the most promising treatment targets and—using GANs—generates molecules (that is, baby drugs) perfectly suited for them. “The result is an explosion in potential drug targets and a much more efficient testing process,” says Zhavoronkov. “AI allows us to do with fifty people what a typical drug company does with five thousand.”
The results have turned what was once a decade-long war into a month-long skirmish.
In late 2018, for example, Insilico was generating novel molecules in fewer than 46 days, and this included not just the initial discovery, but also the synthesis of the drug and its experimental validation in computer simulations.
Right now, they’re using the system to hunt down new drugs for cancer, aging, fibrosis, Parkinson’s, Alzheimer’s, ALS, diabetes, and many others. The first drug to result from this work, a treatment for hair loss, is slated to start Phase I trials by the end of 2020.
They’re also in the early stages of using AI to predict the outcomes of clinical trials in advance of the trial. If successful, this technique will enable researchers to strip a bundle of time and money out of the traditional testing process.
Protein Folding
Beyond inventing new drugs, AI is also being used by other scientists to identify new drug targets—that is, the place to which a drug binds in the body and another key part of the drug discovery process.
Between 1980 and 2006, despite an annual investment of $30 billion, researchers only managed to find about five new drug targets a year. The trouble is complexity. Most potential drug targets are proteins, and a protein’s structure—meaning the way a 2D sequence of amino acids folds into a 3D protein—determines its function.
But a protein with merely a hundred amino acids (a rather small protein) can produce a googol-cubed worth of potential shapes—that’s a one followed by three hundred zeroes. This is also why protein-folding has long been considered an intractably hard problem for even the most powerful of supercomputers.
Back in 1994, to monitor supercomputers’ progress in protein-folding, a biannual competition was created. Until 2018, success was fairly rare. But then the creators of DeepMind turned their neural networks loose on the problem. They created an AI that mines enormous datasets to determine the most likely distance between a protein’s base pairs and the angles of their chemical bonds—aka, the basics of protein-folding. They called it AlphaFold.
On its first foray into the competition, contestant AIs were given 43 protein-folding problems to solve. AlphaFold got 25 right. The second-place team managed a meager three. By predicting the elusive ways in which various proteins fold on the basis of their amino acid sequences, AlphaFold may soon have a tremendous impact in aiding drug discovery and fighting some of today’s most intractable diseases.
Drug Delivery
Another theater of war for improved drugs is the realm of drug delivery. Even here, converging exponential technologies are paving the way for massive implications in both human health and industry shifts.
One key contender is CRISPR, the fast-advancing gene-editing technology that stands to revolutionize synthetic biology and treatment of genetically linked diseases. And researchers have now demonstrated how this tool can be applied to create materials that shape-shift on command. Think: materials that dissolve instantaneously when faced with a programmed stimulus, releasing a specified drug at a highly targeted location.
Yet another potential boon for targeted drug delivery is nanotechnology, whereby medical nanorobots have now been used to fight incidences of cancer. In a recent review of medical micro- and nanorobotics, lead authors (from the University of Texas at Austin and University of California, San Diego) found numerous successful tests of in vivo operation of medical micro- and nanorobots.
Drugs From the Future
Covid-19 is uniting the global scientific community with its urgency, prompting scientists to cast aside nation-specific territorialism, research secrecy, and academic publishing politics in favor of expedited therapeutic and vaccine development efforts. And in the wake of rapid acceleration across healthcare technologies, Big Pharma is an area worth watching right now, no matter your industry. Converging technologies will soon enable extraordinary strides in longevity and disease prevention, with companies like Insilico leading the charge.
Riding the convergence of massive datasets, skyrocketing computational power, quantum computing, cognitive surplus capabilities, and remarkable innovations in AI, we are not far from a world in which personalized drugs, delivered directly to specified targets, will graduate from science fiction to the standard of care.
Rejuvenational biotechnology will be commercially available sooner than you think. When I asked Alex for his own projection, he set the timeline at “maybe 20 years—that’s a reasonable horizon for tangible rejuvenational biotechnology.”
How might you use an extra 20 or more healthy years in your life? What impact would you be able to make?
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: andreas160578 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