Tag Archives: Drug
#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
#437242 Robot jaws show medicated chewing gum ...
Medicated chewing gum has been recognized as a new advanced drug delivery method but currently there is no gold standard for testing drugs released from chewing gum in vitro. New research has shown a chewing robot with built-in humanoid jaws could provide opportunities for pharmaceutical companies to develop medicated chewing gum. Continue reading
Posted in Human Robots
#437236 Why We Need Mass Automation to ...
The scale of goods moving around the planet at any moment is staggering. Raw materials are dug up in one country, spun into parts and pieces in another, and assembled into products in a third. Crossing oceans and continents, they find their way to a local store or direct to your door.
Magically, a roll of toilet paper, power tool, or tube of toothpaste is there just when you need it.
Even more staggering is that this whole system, the global supply chain, works so well that it’s effectively invisible most of the time. Until now, that is. The pandemic has thrown a floodlight on the inner workings of this modern wonder—and it’s exposed massive vulnerabilities.
The e-commerce supply chain is an instructive example. As the world went into lockdown, and everything non-essential went online, demand for digital fulfillment skyrocketed.
Even under “normal” conditions, most e-commerce warehouses were struggling to meet demand. But Covid-19 has further strained the ability to cope with shifting supply, an unprecedented tidal wave of orders, and labor shortages. Local stores are running out of key products. Online grocers and e-commerce platforms are suspending some home deliveries, restricting online purchases of certain items, and limiting new customers. The whole system is being severely tested.
Why? Despite an abundance of 21st century technology, we’re stuck in the 20th century.
Today’s supply chain consists of fleets of ships, trucks, warehouses, and importantly, people scattered around the world. While there are some notable instances of advanced automation, the overwhelming majority of work is still manual, resembling a sort of human-powered bucket brigade, with people wandering around warehouses or standing alongside conveyor belts. Each package of diapers or bottle of detergent ordered by an online customer might be touched dozens of times by warehouse workers before finding its way into a box delivered to a home.
The pandemic has proven the critical need for innovation due to increased demand, concerns about the health and safety of workers, and traceability and safety of products and services.
At the 2020 World Economic Forum, there was much discussion about the ongoing societal transformation in which humans and machines work in tandem, automating and augmenting the way we get things done. At the time, pre-pandemic, debate trended toward skepticism and fear of job losses, with some even questioning the ethics and need for these technologies.
Now, we see things differently. To make the global supply chain more resilient to shocks like Covid-19, we must look to technology.
Perfecting the Global Supply Chain: The Massive ‘Matter Router’
Technology has faced and overcome similar challenges in the past.
World War II, for example, drove innovation in techniques for rapid production of many products on a large scale, including penicillin. We went from the availability of one dose of the drug in 1941, to four million sterile packages of the drug every month four years later.
Similarly, today’s companies, big and small, are looking to automation, robotics, and AI to meet the pandemic head on. These technologies are crucial to scaling the infrastructure that will fulfill most of the world’s e-commerce and food distribution needs.
You can think of this new infrastructure as a rapidly evolving “matter router” that will employ increasingly complex robotic systems to move products more freely and efficiently.
Robots powered by specialized AI software, for example, are already learning to adapt to changes in the environment, using the most recent advances in industrial robotics and machine learning. When customers suddenly need to order dramatically new items, these robots don’t need to stop or be reprogrammed. They can perform new tasks by learning from experience using low-cost camera systems and deep learning for visual and image recognition.
These more flexible robots can work around the clock, helping make facilities less sensitive to sudden changes in workforce and customer demand and strengthening the supply chain.
Today, e-commerce is roughly 12% of retail sales in the US and is expected to rise well beyond 25% within the decade, fueled by changes in buying habits. However, analysts have begun to consider whether the current crisis might cause permanent jumps in those numbers, as it has in the past (for instance with the SARS epidemic in China in 2003). Whatever happens, the larger supply chain will benefit from greater, more flexible automation, especially during global crises.
We must create what Hamza Mudassire of the University of Cambridge calls a “resilient ecosystem that links multiple buyers with multiple vendors, across a mesh of supply chains.” This ecosystem must be backed by robust, efficient, and scalable automation that uses robotics, autonomous vehicles, and the Internet of Things to help track the flow of goods through the supply chain.
The good news? We can accomplish this with technologies we have today.
Image credit: Guillaume Bolduc / Unsplash Continue reading
Posted in Human Robots
#437222 China and AI: What the World Can Learn ...
China announced in 2017 its ambition to become the world leader in artificial intelligence (AI) by 2030. While the US still leads in absolute terms, China appears to be making more rapid progress than either the US or the EU, and central and local government spending on AI in China is estimated to be in the tens of billions of dollars.
The move has led—at least in the West—to warnings of a global AI arms race and concerns about the growing reach of China’s authoritarian surveillance state. But treating China as a “villain” in this way is both overly simplistic and potentially costly. While there are undoubtedly aspects of the Chinese government’s approach to AI that are highly concerning and rightly should be condemned, it’s important that this does not cloud all analysis of China’s AI innovation.
The world needs to engage seriously with China’s AI development and take a closer look at what’s really going on. The story is complex and it’s important to highlight where China is making promising advances in useful AI applications and to challenge common misconceptions, as well as to caution against problematic uses.
Nesta has explored the broad spectrum of AI activity in China—the good, the bad, and the unexpected.
The Good
China’s approach to AI development and implementation is fast-paced and pragmatic, oriented towards finding applications which can help solve real-world problems. Rapid progress is being made in the field of healthcare, for example, as China grapples with providing easy access to affordable and high-quality services for its aging population.
Applications include “AI doctor” chatbots, which help to connect communities in remote areas with experienced consultants via telemedicine; machine learning to speed up pharmaceutical research; and the use of deep learning for medical image processing, which can help with the early detection of cancer and other diseases.
Since the outbreak of Covid-19, medical AI applications have surged as Chinese researchers and tech companies have rushed to try and combat the virus by speeding up screening, diagnosis, and new drug development. AI tools used in Wuhan, China, to tackle Covid-19 by helping accelerate CT scan diagnosis are now being used in Italy and have been also offered to the NHS in the UK.
The Bad
But there are also elements of China’s use of AI that are seriously concerning. Positive advances in practical AI applications that are benefiting citizens and society don’t detract from the fact that China’s authoritarian government is also using AI and citizens’ data in ways that violate privacy and civil liberties.
Most disturbingly, reports and leaked documents have revealed the government’s use of facial recognition technologies to enable the surveillance and detention of Muslim ethnic minorities in China’s Xinjiang province.
The emergence of opaque social governance systems that lack accountability mechanisms are also a cause for concern.
In Shanghai’s “smart court” system, for example, AI-generated assessments are used to help with sentencing decisions. But it is difficult for defendants to assess the tool’s potential biases, the quality of the data, and the soundness of the algorithm, making it hard for them to challenge the decisions made.
China’s experience reminds us of the need for transparency and accountability when it comes to AI in public services. Systems must be designed and implemented in ways that are inclusive and protect citizens’ digital rights.
The Unexpected
Commentators have often interpreted the State Council’s 2017 Artificial Intelligence Development Plan as an indication that China’s AI mobilization is a top-down, centrally planned strategy.
But a closer look at the dynamics of China’s AI development reveals the importance of local government in implementing innovation policy. Municipal and provincial governments across China are establishing cross-sector partnerships with research institutions and tech companies to create local AI innovation ecosystems and drive rapid research and development.
Beyond the thriving major cities of Beijing, Shanghai, and Shenzhen, efforts to develop successful innovation hubs are also underway in other regions. A promising example is the city of Hangzhou, in Zhejiang Province, which has established an “AI Town,” clustering together the tech company Alibaba, Zhejiang University, and local businesses to work collaboratively on AI development. China’s local ecosystem approach could offer interesting insights to policymakers in the UK aiming to boost research and innovation outside the capital and tackle longstanding regional economic imbalances.
China’s accelerating AI innovation deserves the world’s full attention, but it is unhelpful to reduce all the many developments into a simplistic narrative about China as a threat or a villain. Observers outside China need to engage seriously with the debate and make more of an effort to understand—and learn from—the nuances of what’s really happening.
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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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