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#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.
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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
#436466 How Two Robots Learned to Grill and ...
The list of things robots can do seems to be growing by the week. They can play sports, help us explore outer space and the deep sea, take over some of our boring everyday tasks, and even assemble Ikea furniture.
Now they can add one more accomplishment to the list: grilling and serving a hot dog.
It seems like a pretty straightforward task, and as far as grilling goes, hot dogs are about as easy as it gets (along with, maybe, burgers? Hot dogs require more rotation, but it’s easier to tell when they’re done since they’re lighter in color).
Let’s paint a picture: you’re manning the grill at your family’s annual Fourth of July celebration. You’ve got a 10-pack of plump, juicy beef franks and a hungry crowd of relatives whose food-to-alcohol ratio is getting pretty skewed—they need some solid calories, pronto. What are the steps you need to take to get those franks from package to plate?
Each one needs to be placed on the grill, rotated every couple minutes for even cooking, removed from the grill when you deem it’s done, then—if you’re the kind of guy or gal who goes the extra mile—placed in a bun and dressed with ketchup, mustard, pickles, and the like before being handed over to salivating, too-loud Uncle Hector or sweet, bored Cousin Margaret.
While carrying out your grillmaster duties, you know better than to drop the hot dogs on the ground, leave them cooking on one side for too long, squeeze them to the point of breaking or bursting, and any other hot-dog-ruining amateur moves.
But for a robot, that’s a lot to figure out, especially if they have no prior knowledge of grilling hot dogs (which, well, most robots don’t).
As described in a paper published in this week’s Science Robotics, a team from Boston University programmed two robotic arms to use reinforcement learning—a branch of machine learning in which software gathers information about its environment then learns from it by replaying its experiences and incorporating rewards—to cook and serve hot dogs.
The team used a set of formulas to specify and combine tasks (“pick up hot dog and place on the grill”), meet safety requirements (“always avoid collisions”), and incorporate general prior knowledge (“you cannot pick up another hot dog if you are already holding one”).
Baxter and Jaco—as the two robots were dubbed—were trained through computer simulations. The paper’s authors emphasized their use of what they call a “formal specification language” for training the software, with the aim of generating easily-interpretable task descriptions. In reinforcement learning, they explain, being able to understand how a reward function influences an AI’s learning process is a key component in understanding the system’s behavior—but most systems lack this quality, and are thus likely to be lumped into the ‘black box’ of AI.
The robots’ decisions throughout the hot dog prep process—when to turn a hot dog, when to take it off the grill, and so on—are, the authors write, “easily interpretable from the beginning because the language is very similar to plain English.”
Besides being a step towards more explainable AI systems, Baxter and Jaco are another example of fast-food robots—following in the footsteps of their burger and pizza counterparts—that may take over some repetitive manual tasks currently performed by human workers. As robots’ capabilities improve through incremental progress like this, they’ll be able to take on additional tasks.
In a not-so-distant future, then, you just may find yourself throwing back drinks with Uncle Hector and Cousin Margaret while your robotic replacement mans the grill, churning out hot dogs that are perfectly cooked every time.
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Posted in Human Robots
#436174 How Selfish Are You? It Matters for ...
Our personalities impact almost everything we do, from the career path we choose to the way we interact with others to how we spend our free time.
But what about the way we drive—could personality be used to predict whether a driver will cut someone off, speed, or, say, zoom through a yellow light instead of braking?
There must be something to the idea that those of us who are more mild-mannered are likely to drive a little differently than the more assertive among us. At least, that’s what a team from MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) is betting on.
“Working with and around humans means figuring out their intentions to better understand their behavior,” said graduate student Wilko Schwarting, lead author on the paper published this week in Proceedings of the National Academy of Sciences. “People’s tendencies to be collaborative or competitive often spills over into how they behave as drivers. In this paper we sought to understand if this was something we could actually quantify.”
The team is building a model that classifies drivers according to how selfish or selfless they are, then uses that classification to help predict how drivers will behave on the road. Ideally, the system will help improve safety for self-driving cars by integrating a degree of ‘humanity’ into how their software perceives its surroundings; right now, human drivers and their cars are just another object, not much different than a tree or a sign.
But unlike trees and signs, humans have behavioral patterns and motivations. For greater success on roads that are still dominated by us mercurial humans, the CSAIL team believes, driverless cars should take our personalities into account.
How Selfish Are You?
About how important is your own well-being to you vs. the well-being of other people? It’s a hard question to answer without specifying who the other people are; your answer would likely differ if we’re talking about your friends, loved ones, strangers, or people you actively dislike.
In social psychology, social value orientation (SVO) refers to people’s preferences for allocating resources between themselves and others. The two broad categories people can fall into are pro-social (people who are more cooperative, and expect cooperation from others) and pro-self (pretty self-explanatory: “Me first!”).
Based on drivers’ behavior in two different road scenarios—merging and making a left turn—the CSAIL team’s model classified drivers as pro-social or egoistic. Slowing down to let someone merge into your lane in front of you would earn you a pro-social classification, while cutting someone off or not slowing down to allow a left turn would make you egoistic.
On the Road
The system then uses these classifications to model and predict drivers’ behavior. The team demonstrated that using their model, errors in predicting the behavior of other cars were reduced by 25 percent.
In a left-turn simulation, for example, their car would wait when an approaching car had an egoistic driver, but go ahead and make the turn when the other driver was prosocial. Similarly, if a self-driving car is trying to merge into the left lane and it’s identified the drivers in that lane as egoistic, it will assume they won’t slow down to let it in, and will wait to merge behind them. If, on the other hand, the self-driving car knows that the human drivers in the left lane are prosocial, it will attempt to merge between them since they’re likely to let it in.
So how does this all translate to better safety?
It’s essentially a starting point for imbuing driverless cars with some of the abilities and instincts that are innate to humans. If you’re driving down the highway and you see a car swerving outside its lane, you’ll probably distance yourself from that car because you know it’s more likely to cause an accident. Our senses take in information we can immediately interpret and act on, and this includes predictions about what might happen based on observations of what just happened. Our observations can clue us in to a driver’s personality (the swerver must be careless) or simply to the circumstances of a given moment (the swerver was texting).
But right now, self-driving cars assume all human drivers behave the same way, and they have no mechanism for incorporating observations about behavioral differences between drivers into their decisions.
“Creating more human-like behavior in autonomous vehicles (AVs) is fundamental for the safety of passengers and surrounding vehicles, since behaving in a predictable manner enables humans to understand and appropriately respond to the AV’s actions,” said Schwarting.
Though it may feel a bit unsettling to think of an algorithm lumping you into a category and driving accordingly around you, maybe it’s less unsettling than thinking of self-driving cars as pre-programmed, oblivious robots unable to adapt to different driving styles.
The team’s next step is to apply their model to pedestrians, bikes, and other agents frequently found in driving environments. They also plan to look into other robotic systems acting among people, like household robots, and integrating social value orientation into their algorithms.
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Posted in Human Robots