Tag Archives: Defense
#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
#436578 AI Just Discovered a New Antibiotic to ...
Penicillin, one of the greatest discoveries in the history of medicine, was a product of chance.
After returning from summer vacation in September 1928, bacteriologist Alexander Fleming found a colony of bacteria he’d left in his London lab had sprouted a fungus. Curiously, wherever the bacteria contacted the fungus, their cell walls broke down and they died. Fleming guessed the fungus was secreting something lethal to the bacteria—and the rest is history.
Fleming’s discovery of penicillin and its later isolation, synthesis, and scaling in the 1940s released a flood of antibiotic discoveries in the next few decades. Bacteria and fungi had been waging an ancient war against each other, and the weapons they’d evolved over eons turned out to be humanity’s best defense against bacterial infection and disease.
In recent decades, however, the flood of new antibiotics has slowed to a trickle.
Their development is uneconomical for drug companies, and the low-hanging fruit has long been picked. We’re now facing the emergence of strains of super bacteria resistant to one or more antibiotics and an aging arsenal to fight them with. Gone unchallenged, an estimated 700,000 deaths worldwide due to drug resistance could rise to as many as 10 million in 2050.
Increasingly, scientists warn the tide is turning, and we need a new strategy to keep pace with the remarkably quick and boundlessly creative tactics of bacterial evolution.
But where the golden age of antibiotics was sparked by serendipity, human intelligence, and natural molecular weapons, its sequel may lean on the uncanny eye of artificial intelligence to screen millions of compounds—and even design new ones—in search of the next penicillin.
Hal Discovers a Powerful Antibiotic
In a paper published this week in the journal, Cell, MIT researchers took a step in this direction. The team says their machine learning algorithm discovered a powerful new antibiotic.
Named for the AI in 2001: A Space Odyssey, the antibiotic, halicin, successfully wiped out dozens of bacterial strains, including some of the most dangerous drug-resistant bacteria on the World Health Organization’s most wanted list. The bacteria also failed to develop resistance to E. coli during a month of observation, in stark contrast to existing antibiotic ciprofloxacin.
“In terms of antibiotic discovery, this is absolutely a first,” Regina Barzilay, a senior author on the study and computer science professor at MIT, told The Guardian.
The algorithm that discovered halicin was trained on the molecular features of 2,500 compounds. Nearly half were FDA-approved drugs, and another 800 naturally occurring. The researchers specifically tuned the algorithm to look for molecules with antibiotic properties but whose structures would differ from existing antibiotics (as halicin’s does). Using another machine learning program, they screened the results for those likely to be safe for humans.
Early study suggests halicin attacks the bacteria’s cell membranes, disrupting their ability to produce energy. Protecting the cell membrane from halicin might take more than one or two genetic mutations, which could account for its impressive ability to prevent resistance.
“I think this is one of the more powerful antibiotics that has been discovered to date,” James Collins, an MIT professor of bioengineering and senior author told The Guardian. “It has remarkable activity against a broad range of antibiotic-resistant pathogens.”
Beyond tests in petri-dish bacterial colonies, the team also tested halicin in mice. The antibiotic cleared up infections of a strain of bacteria resistant to all known antibiotics in a day. The team plans further study in partnership with a pharmaceutical company or nonprofit, and they hope to eventually prove it safe and effective for use in humans.
This last bit remains the trickiest step, given the cost of getting a new drug approved. But Collins hopes algorithms like theirs will help. “We could dramatically reduce the cost required to get through clinical trials,” he told the Financial Times.
A Universe of Drugs Awaits
The bigger story may be what happens next.
How many novel antibiotics await discovery, and how far can AI screening take us? The initial 6,000 compounds scanned by Barzilay and Collins’s team is a drop in the bucket.
They’ve already begun digging deeper by setting the algorithm loose on 100 million molecules from an online library of 1.5 billion compounds called the ZINC15 database. This first search took three days and turned up 23 more candidates that, like halicin, differ structurally from existing antibiotics and may be safe for humans. Two of these—which the team will study further—appear to be especially powerful.
Even more ambitiously, Barzilay hopes the approach can find or even design novel antibiotics that kill bad bacteria with alacrity while sparing the good guys. In this way, a round of antibiotics would cure whatever ails you without taking out your whole gut microbiome in the process.
All this is part of a larger movement to use machine learning algorithms in the long, expensive process of drug discovery. Other players in the area are also training AI on the vast possibility space of drug-like compounds. Last fall, one of the leaders in the area, Insilico, was challenged by a partner to see just how fast their method could do the job. The company turned out a new a proof-of-concept drug candidate in only 46 days.
The field is still developing, however, and it has yet to be seen exactly how valuable these approaches will be in practice. Barzilay is optimistic though.
“There is still a question of whether machine-learning tools are really doing something intelligent in healthcare, and how we can develop them to be workhorses in the pharmaceuticals industry,” she said. “This shows how far you can adapt this tool.”
Image Credit: Halicin (top row) prevented the development of antibiotic resistance in E. coli, while ciprofloxacin (bottom row) did not. Collins Lab at MIT Continue reading
Posted in Human Robots
#436167 Is it Time for Tech to Stop Moving Fast ...
On Monday, I attended the 2019 Fall Conference of Stanford’s Institute for Human Centered Artificial Intelligence (HAI). That same night I watched the Season 6 opener for the HBO TV show Silicon Valley. And the debates featured in both surrounded the responsibility of tech companies for the societal effects of the technologies they produce. The two events have jumbled together in my mind, perhaps because I was in a bit of a brain fog, thanks to the nasty combination of a head cold and the smoke that descended on Silicon Valley from the northern California wildfires. But perhaps that mixture turned out to be a good thing.
What is clear, in spite of the smoke, is that this issue is something a lot of people are talking about, inside and outside of Silicon Valley (witness the viral video of Rep. Alexandria Ocasio-Cortez (D-NY) grilling Facebook CEO Mark Zuckerberg).
So, to add to that conversation, here’s my HBO Silicon Valley/Stanford HAI conference mashup.
Silicon Valley’s fictional CEO Richard Hendriks, in the opening scene of the episode, tells Congress that Facebook, Google, and Amazon only care about exploiting personal data for profit. He states:
“These companies are kings, and they rule over kingdoms far larger than any nation in history.”
Meanwhile Marietje Schaake, former member of the European Parliament and a fellow at HAI, told the conference audience of 900:
“There is a lot of power in the hands of few actors—Facebook decides who is a news source, Microsoft will run the defense department’s cloud…. I believe we need a deeper debate about which tasks need to stay in the hands of the public.”
Eric Schmidt, former CEO and executive chairman of Google, agreed. He says:
“It is important that we debate now the ethics of what we are doing, and the impact of the technology that we are building.”
Stanford Associate Professor Ge Wang, also speaking at the HAI conference, pointed out:
“‘Doing no harm’ is a vital goal, and it is not easy. But it is different from a proactive goal, to ‘do good.’”
Had Silicon Valley’s Hendricks been there, he would have agreed. He said in the episode:
“Just because it’s successful, doesn’t mean it’s good. Hiroshima was a successful implementation.”
The speakers at the HAI conference discussed the implications of moving fast and breaking things, of putting untested and unregulated technology into the world now that we know that things like public trust and even democracy can be broken.
Google’s Schmidt told the HAI audience:
“I don’t think that everything that is possible should be put into the wild in society, we should answer the question, collectively, how much risk are we willing to take.
And Silicon Valley denizens real and fictional no longer think it’s OK to just say sorry afterwards. Says Schmidt:
“When you ask Facebook about various scandals, how can they still say ‘We are very sorry; we have a lot of learning to do.’ This kind of naiveté stands out of proportion to the power tech companies have. With great power should come great responsibility, or at least modesty.”
Schaake argued:
“We need more guarantees, institutions, and policies than stated good intentions. It’s about more than promises.”
Fictional CEO Hendricks thinks saying sorry is a cop-out as well. In the episode, a developer admits that his app collected user data in spite of Hendricks assuring Congress that his company doesn’t do that:
“You didn’t know at the time,” the developer says. “Don’t beat yourself up about it. But in the future, stop saying it. Or don’t; I don’t care. Maybe it will be like Google saying ‘Don’t be evil,’ or Facebook saying ‘I’m sorry, we’ll do better.’”
Hendricks doesn’t buy it:
“This stops now. I’m the boss, and this is over.”
(Well, he is fictional.)
How can government, the tech world, and the general public address this in a more comprehensive way? Out in the real world, the “what to do” discussion at Stanford HAI surrounded regulation—how much, what kind, and when.
Says the European Parliament’s Schaake:
“An often-heard argument is that government should refrain from regulating tech because [regulation] will stifle innovation. [That argument] implies that innovation is more important than democracy or the rule of law. Our problems don’t stem from over regulation, but under regulation of technologies.”
But when should that regulation happen. Stanford provost emeritus John Etchemendy, speaking from the audience at the HAI conference, said:
“I’ve been an advocate of not trying to regulate before you understand it. Like San Francisco banning of use of facial recognition is not a good example of regulation; there are uses of facial recognition that we should allow. We want regulations that are just right, that prevent the bad things and allow the good things. So we are going to get it wrong either way, if we regulate to soon or hold off, we will get some things wrong.”
Schaake would opt for regulating sooner rather than later. She says that she often hears the argument that it is too early to regulate artificial intelligence—as well as the argument that it is too late to regulate ad-based political advertising, or online privacy. Neither, to her, makes sense. She told the HAI attendees:
“We need more than guarantees than stated good intentions.”
U.S. Chief Technology Officer Michael Kratsios would go with later rather than sooner. (And, yes, the country has a CTO. President Barack Obama created the position in 2009; Kratsios is the fourth to hold the office and the first under President Donald Trump. He was confirmed in August.) Also speaking at the HAI conference, Kratsios argued:
“I don’t think we should be running to regulate anything. We are a leader [in technology] not because we had great regulations, but we have taken a free market approach. We have done great in driving innovation in technologies that are born free, like the Internet. Technologies born in captivity, like autonomous vehicles, lag behind.”
In the fictional world of HBO’s Silicon Valley, startup founder Hendricks has a solution—a technical one of course: the decentralized Internet. He tells Congress:
“The way we win is by creating a new, decentralized Internet, one where the behavior of companies like this will be impossible, forever. Where it is the users, not the kings, who have sovereign control over their data. I will help you build an Internet that is of the people, by the people, and for the people.”
(This is not a fictional concept, though it is a long way from wide use. Also called the decentralized Web, the concept takes the content on today’s Web and fragments it, and then replicates and scatters those fragments to hosts around the world, increasing privacy and reducing the ability of governments to restrict access.)
If neither regulation nor technology comes to make the world safe from the unforeseen effects of new technologies, there is one more hope, according to Schaake: the millennials and subsequent generations.
Tech companies can no longer pursue growth at all costs, not if they want to keep attracting the talent they need, says Schaake. She noted that, “the young generation looks at the environment, at homeless on the streets,” and they expect their companies to tackle those and other issues and make the world a better place. Continue reading
Posted in Human Robots