Tag Archives: 2015

#434854 New Lifelike Biomaterial Self-Reproduces ...

Life demands flux.

Every living organism is constantly changing: cells divide and die, proteins build and disintegrate, DNA breaks and heals. Life demands metabolism—the simultaneous builder and destroyer of living materials—to continuously upgrade our bodies. That’s how we heal and grow, how we propagate and survive.

What if we could endow cold, static, lifeless robots with the gift of metabolism?

In a study published this month in Science Robotics, an international team developed a DNA-based method that gives raw biomaterials an artificial metabolism. Dubbed DASH—DNA-based assembly and synthesis of hierarchical materials—the method automatically generates “slime”-like nanobots that dynamically move and navigate their environments.

Like humans, the artificial lifelike material used external energy to constantly change the nanobots’ bodies in pre-programmed ways, recycling their DNA-based parts as both waste and raw material for further use. Some “grew” into the shape of molecular double-helixes; others “wrote” the DNA letters inside micro-chips.

The artificial life forms were also rather “competitive”—in quotes, because these molecular machines are not conscious. Yet when pitted against each other, two DASH bots automatically raced forward, crawling in typical slime-mold fashion at a scale easily seen under the microscope—and with some iterations, with the naked human eye.

“Fundamentally, we may be able to change how we create and use the materials with lifelike characteristics. Typically materials and objects we create in general are basically static… one day, we may be able to ‘grow’ objects like houses and maintain their forms and functions autonomously,” said study author Dr. Shogo Hamada to Singularity Hub.

“This is a great study that combines the versatility of DNA nanotechnology with the dynamics of living materials,” said Dr. Job Boekhoven at the Technical University of Munich, who was not involved in the work.

Dissipative Assembly
The study builds on previous ideas on how to make molecular Lego blocks that essentially assemble—and destroy—themselves.

Although the inspiration came from biological metabolism, scientists have long hoped to cut their reliance on nature. At its core, metabolism is just a bunch of well-coordinated chemical reactions, programmed by eons of evolution. So why build artificial lifelike materials still tethered by evolution when we can use chemistry to engineer completely new forms of artificial life?

Back in 2015, for example, a team led by Boekhoven described a way to mimic how our cells build their internal “structural beams,” aptly called the cytoskeleton. The key here, unlike many processes in nature, isn’t balance or equilibrium; rather, the team engineered an extremely unstable system that automatically builds—and sustains—assemblies from molecular building blocks when given an external source of chemical energy.

Sound familiar? The team basically built molecular devices that “die” without “food.” Thanks to the laws of thermodynamics (hey ya, Newton!), that energy eventually dissipates, and the shapes automatically begin to break down, completing an artificial “circle of life.”

The new study took the system one step further: rather than just mimicking synthesis, they completed the circle by coupling the building process with dissipative assembly.

Here, the “assembling units themselves are also autonomously created from scratch,” said Hamada.

DNA Nanobots
The process of building DNA nanobots starts on a microfluidic chip.

Decades of research have allowed researchers to optimize DNA assembly outside the body. With the help of catalysts, which help “bind” individual molecules together, the team found that they could easily alter the shape of the self-assembling DNA bots—which formed fiber-like shapes—by changing the structure of the microfluidic chambers.

Computer simulations played a role here too: through both digital simulations and observations under the microscope, the team was able to identify a few critical rules that helped them predict how their molecules self-assemble while navigating a maze of blocking “pillars” and channels carved onto the microchips.

This “enabled a general design strategy for the DASH patterns,” they said.

In particular, the whirling motion of the fluids as they coursed through—and bumped into—ridges in the chips seems to help the DNA molecules “entangle into networks,” the team explained.

These insights helped the team further develop the “destroying” part of metabolism. Similar to linking molecules into DNA chains, their destruction also relies on enzymes.

Once the team pumped both “generation” and “degeneration” enzymes into the microchips, along with raw building blocks, the process was completely autonomous. The simultaneous processes were so lifelike that the team used a metric commonly used in robotics, finite-state automation, to measure the behavior of their DNA nanobots from growth to eventual decay.

“The result is a synthetic structure with features associated with life. These behaviors include locomotion, self-regeneration, and spatiotemporal regulation,” said Boekhoven.

Molecular Slime Molds
Just witnessing lifelike molecules grow in place like the dance move running man wasn’t enough.

In their next experiments, the team took inspiration from slugs to program undulating movements into their DNA bots. Here, “movement” is actually a sort of illusion: the machines “moved” because their front ends kept regenerating, whereas their back ends degenerated. In essence, the molecular slime was built from linking multiple individual “DNA robot-like” units together: each unit receives a delayed “decay” signal from the head of the slime in a way that allowed the whole artificial “organism” to crawl forward, against the steam of fluid flow.

Here’s the fun part: the team eventually engineered two molecular slime bots and pitted them against each other, Mario Kart-style. In these experiments, the faster moving bot alters the state of its competitor to promote “decay.” This slows down the competitor, allowing the dominant DNA nanoslug to win in a race.

Of course, the end goal isn’t molecular podracing. Rather, the DNA-based bots could easily amplify a given DNA or RNA sequence, making them efficient nano-diagnosticians for viral and other infections.

The lifelike material can basically generate patterns that doctors can directly ‘see’ with their eyes, which makes DNA or RNA molecules from bacteria and viruses extremely easy to detect, the team said.

In the short run, “the detection device with this self-generating material could be applied to many places and help people on site, from farmers to clinics, by providing an easy and accurate way to detect pathogens,” explained Hamaga.

A Futuristic Iron Man Nanosuit?
I’m letting my nerd flag fly here. In Avengers: Infinity Wars, the scientist-engineer-philanthropist-playboy Tony Stark unveiled a nanosuit that grew to his contours when needed and automatically healed when damaged.

DASH may one day realize that vision. For now, the team isn’t focused on using the technology for regenerating armor—rather, the dynamic materials could create new protein assemblies or chemical pathways inside living organisms, for example. The team also envisions adding simple sensing and computing mechanisms into the material, which can then easily be thought of as a robot.

Unlike synthetic biology, the goal isn’t to create artificial life. Rather, the team hopes to give lifelike properties to otherwise static materials.

“We are introducing a brand-new, lifelike material concept powered by its very own artificial metabolism. We are not making something that’s alive, but we are creating materials that are much more lifelike than have ever been seen before,” said lead author Dr. Dan Luo.

“Ultimately, our material may allow the construction of self-reproducing machines… artificial metabolism is an important step toward the creation of ‘artificial’ biological systems with dynamic, lifelike capabilities,” added Hamada. “It could open a new frontier in robotics.”

Image Credit: A timelapse image of DASH, by Jeff Tyson at Cornell University. Continue reading

Posted in Human Robots

#434792 Extending Human Longevity With ...

Lizards can regrow entire limbs. Flatworms, starfish, and sea cucumbers regrow entire bodies. Sharks constantly replace lost teeth, often growing over 20,000 teeth throughout their lifetimes. How can we translate these near-superpowers to humans?

The answer: through the cutting-edge innovations of regenerative medicine.

While big data and artificial intelligence transform how we practice medicine and invent new treatments, regenerative medicine is about replenishing, replacing, and rejuvenating our physical bodies.

In Part 5 of this blog series on Longevity and Vitality, I detail three of the regenerative technologies working together to fully augment our vital human organs.

Replenish: Stem cells, the regenerative engine of the body
Replace: Organ regeneration and bioprinting
Rejuvenate: Young blood and parabiosis

Let’s dive in.

Replenish: Stem Cells – The Regenerative Engine of the Body
Stem cells are undifferentiated cells that can transform into specialized cells such as heart, neurons, liver, lung, skin and so on, and can also divide to produce more stem cells.

In a child or young adult, these stem cells are in large supply, acting as a built-in repair system. They are often summoned to the site of damage or inflammation to repair and restore normal function.

But as we age, our supply of stem cells begins to diminish as much as 100- to 10,000-fold in different tissues and organs. In addition, stem cells undergo genetic mutations, which reduce their quality and effectiveness at renovating and repairing your body.

Imagine your stem cells as a team of repairmen in your newly constructed mansion. When the mansion is new and the repairmen are young, they can fix everything perfectly. But as the repairmen age and reduce in number, your mansion eventually goes into disrepair and finally crumbles.

What if you could restore and rejuvenate your stem cell population?

One option to accomplish this restoration and rejuvenation is to extract and concentrate your own autologous adult stem cells from places like your adipose (or fat) tissue or bone marrow.

These stem cells, however, are fewer in number and have undergone mutations (depending on your age) from their original ‘software code.’ Many scientists and physicians now prefer an alternative source, obtaining stem cells from the placenta or umbilical cord, the leftovers of birth.

These stem cells, available in large supply and expressing the undamaged software of a newborn, can be injected into joints or administered intravenously to rejuvenate and revitalize.

Think of these stem cells as chemical factories generating vital growth factors that can help to reduce inflammation, fight autoimmune disease, increase muscle mass, repair joints, and even revitalize skin and grow hair.

Over the last decade, the number of publications per year on stem cell-related research has increased 40x, and the stem cell market is expected to increase to $297 billion by 2022.

Rising research and development initiatives to develop therapeutic options for chronic diseases and growing demand for regenerative treatment options are the most significant drivers of this budding industry.

Biologists led by Kohji Nishida at Osaka University in Japan have discovered a new way to nurture and grow the tissues that make up the human eyeball. The scientists are able to grow retinas, corneas, the eye’s lens, and more, using only a small sample of adult skin.

In a Stanford study, seven of 18 stroke victims who agreed to stem cell treatments showed remarkable motor function improvements. This treatment could work for other neurodegenerative conditions such as Alzheimer’s, Parkinson’s, and ALS.

Doctors from the USC Neurorestoration Center and Keck Medicine of USC injected stem cells into the damaged cervical spine of a recently paralyzed 21-year-old man. Three months later, he showed dramatic improvement in sensation and movement of both arms.

In 2019, doctors in the U.K. cured a patient with HIV for the second time ever thanks to the efficacy of stem cells. After giving the cancer patient (who also had HIV) an allogeneic haematopoietic (e.g. blood) stem cell treatment for his Hodgkin’s lymphoma, the patient went into long-term HIV remission—18 months and counting at the time of the study’s publication.

Replace: Organ Regeneration and 3D Printing
Every 10 minutes, someone is added to the US organ transplant waiting list, totaling over 113,000 people waiting for replacement organs as of January 2019.

Countless more people in need of ‘spare parts’ never make it onto the waiting list. And on average, 20 people die each day while waiting for a transplant.

As a result, 35 percent of all US deaths (~900,000 people) could be prevented or delayed with access to organ replacements.

The excessive demand for donated organs will only intensify as technologies like self-driving cars make the world safer, given that many organ donors result from auto and motorcycle accidents. Safer vehicles mean less accidents and donations.

Clearly, replacement and regenerative medicine represent a massive opportunity.

Organ Entrepreneurs
Enter United Therapeutics CEO, Dr. Martine Rothblatt. A one-time aerospace entrepreneur (she was the founder of Sirius Satellite Radio), Rothblatt changed careers in the 1990s after her daughter developed a rare lung disease.

Her moonshot today is to create an industry of replacement organs. With an initial focus on diseases of the lung, Rothblatt set out to create replacement lungs. To accomplish this goal, her company United Therapeutics has pursued a number of technologies in parallel.

3D Printing Lungs
In 2017, United teamed up with one of the world’s largest 3D printing companies, 3D Systems, to build a collagen bioprinter and is paying another company, 3Scan, to slice up lungs and create detailed maps of their interior.

This 3D Systems bioprinter now operates according to a method called stereolithography. A UV laser flickers through a shallow pool of collagen doped with photosensitive molecules. Wherever the laser lingers, the collagen cures and becomes solid.

Gradually, the object being printed is lowered and new layers are added. The printer can currently lay down collagen at a resolution of around 20 micrometers, but will need to achieve resolution of a micrometer in size to make the lung functional.

Once a collagen lung scaffold has been printed, the next step is to infuse it with human cells, a process called recellularization.

The goal here is to use stem cells that grow on scaffolding and differentiate, ultimately providing the proper functionality. Early evidence indicates this approach can work.

In 2018, Harvard University experimental surgeon Harald Ott reported that he pumped billions of human cells (from umbilical cords and diced lungs) into a pig lung stripped of its own cells. When Ott’s team reconnected it to a pig’s circulation, the resulting organ showed rudimentary function.

Humanizing Pig Lungs
Another of Rothblatt’s organ manufacturing strategies is called xenotransplantation, the idea of transplanting an animal’s organs into humans who need a replacement.

Given the fact that adult pig organs are similar in size and shape to those of humans, United Therapeutics has focused on genetically engineering pigs to allow humans to use their organs. “It’s actually not rocket science,” said Rothblatt in her 2015 TED talk. “It’s editing one gene after another.”

To accomplish this goal, United Therapeutics made a series of investments in companies such as Revivicor Inc. and Synthetic Genomics Inc., and signed large funding agreements with the University of Maryland, University of Alabama, and New York Presbyterian/Columbia University Medical Center to create xenotransplantation programs for new hearts, kidneys, and lungs, respectively. Rothblatt hopes to see human translation in three to four years.

In preparation for that day, United Therapeutics owns a 132-acre property in Research Triangle Park and built a 275,000-square-foot medical laboratory that will ultimately have the capability to annually produce up to 1,000 sets of healthy pig lungs—known as xenolungs—from genetically engineered pigs.

Lung Ex Vivo Perfusion Systems
Beyond 3D printing and genetically engineering pig lungs, Rothblatt has already begun implementing a third near-term approach to improve the supply of lungs across the US.

Only about 30 percent of potential donor lungs meet transplant criteria in the first place; of those, only about 85 percent of those are usable once they arrive at the surgery center. As a result, nearly 75 percent of possible lungs never make it to the recipient in need.

What if these lungs could be rejuvenated? This concept informs Dr. Rothblatt’s next approach.

In 2016, United Therapeutics invested $41.8 million in TransMedics Inc., an Andover, Massachusetts company that develops ex vivo perfusion systems for donor lungs, hearts, and kidneys.

The XVIVO Perfusion System takes marginal-quality lungs that initially failed to meet transplantation standard-of-care criteria and perfuses and ventilates them at normothermic conditions, providing an opportunity for surgeons to reassess transplant suitability.

Rejuvenate Young Blood and Parabiosis
In HBO’s parody of the Bay Area tech community, Silicon Valley, one of the episodes (Season 4, Episode 5) is named “The Blood Boy.”

In this installment, tech billionaire Gavin Belson (Matt Ross) is meeting with Richard Hendricks (Thomas Middleditch) and his team, speaking about the future of the decentralized internet. A young, muscled twenty-something disrupts the meeting when he rolls in a transfusion stand and silently hooks an intravenous connection between himself and Belson.

Belson then introduces the newcomer as his “transfusion associate” and begins to explain the science of parabiosis: “Regular transfusions of the blood of a younger physically fit donor can significantly retard the aging process.”

While the sitcom is fiction, that science has merit, and the scenario portrayed in the episode is already happening today.

On the first point, research at Stanford and Harvard has demonstrated that older animals, when transfused with the blood of young animals, experience regeneration across many tissues and organs.

The opposite is also true: young animals, when transfused with the blood of older animals, experience accelerated aging. But capitalizing on this virtual fountain of youth has been tricky.

Ambrosia
One company, a San Francisco-based startup called Ambrosia, recently commenced one of the trials on parabiosis. Their protocol is simple: Healthy participants aged 35 and older get a transfusion of blood plasma from donors under 25, and researchers monitor their blood over the next two years for molecular indicators of health and aging.

Ambrosia’s founder Jesse Karmazin became interested in launching a company around parabiosis after seeing impressive data from animals and studies conducted abroad in humans: In one trial after another, subjects experience a reversal of aging symptoms across every major organ system. “The effects seem to be almost permanent,” he said. “It’s almost like there’s a resetting of gene expression.”

Infusing your own cord blood stem cells as you age may have tremendous longevity benefits. Following an FDA press release in February 2019, Ambrosia halted its consumer-facing treatment after several months of operation.

Understandably, the FDA raised concerns about the practice of parabiosis because to date, there is a marked lack of clinical data to support the treatment’s effectiveness.

Elevian
On the other end of the reputability spectrum is a startup called Elevian, spun out of Harvard University. Elevian is approaching longevity with a careful, scientifically validated strategy. (Full Disclosure: I am both an advisor to and investor in Elevian.)

CEO Mark Allen, MD, is joined by a dozen MDs and Ph.Ds out of Harvard. Elevian’s scientific founders started the company after identifying specific circulating factors that may be responsible for the “young blood” effect.

One example: A naturally occurring molecule known as “growth differentiation factor 11,” or GDF11, when injected into aged mice, reproduces many of the regenerative effects of young blood, regenerating heart, brain, muscles, lungs, and kidneys.

More specifically, GDF11 supplementation reduces age-related cardiac hypertrophy, accelerates skeletal muscle repair, improves exercise capacity, improves brain function and cerebral blood flow, and improves metabolism.

Elevian is developing a number of therapeutics that regulate GDF11 and other circulating factors. The goal is to restore our body’s natural regenerative capacity, which Elevian believes can address some of the root causes of age-associated disease with the promise of reversing or preventing many aging-related diseases and extending the healthy lifespan.

Conclusion
In 1992, futurist Leland Kaiser coined the term “regenerative medicine”:

“A new branch of medicine will develop that attempts to change the course of chronic disease and in many instances will regenerate tired and failing organ systems.”

Since then, the powerful regenerative medicine industry has grown exponentially, and this rapid growth is anticipated to continue.

A dramatic extension of the human healthspan is just over the horizon. Soon, we’ll all have the regenerative superpowers previously relegated to a handful of animals and comic books.

What new opportunities open up when anybody, anywhere, and at anytime can regenerate, replenish, and replace entire organs and metabolic systems on command?

Join Me
Abundance-Digital Online Community: I’ve created a Digital/Online community of bold, abundance-minded entrepreneurs called Abundance-Digital. Abundance-Digital is my ‘onramp’ for exponential entrepreneurs – those who want to get involved and play at a higher level. Click here to learn more.

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Posted in Human Robots

#434772 Traditional Higher Education Is Losing ...

Should you go to graduate school? If so, why? If not, what are your alternatives? Millions of young adults across the globe—and their parents and mentors—find themselves asking these questions every year.

Earlier this month, I explored how exponential technologies are rising to meet the needs of the rapidly changing workforce.

In this blog, I’ll dive into a highly effective way to build the business acumen and skills needed to make the most significant impact in these exponential times.

To start, let’s dive into the value of graduate school versus apprenticeship—especially during this time of extraordinarily rapid growth, and the micro-diversification of careers.

The True Value of an MBA
All graduate schools are not created equal.

For complex technical trades like medicine, engineering, and law, formal graduate-level training provides a critical foundation for safe, ethical practice (until these trades are fully augmented by artificial intelligence and automation…).

For the purposes of today’s blog, let’s focus on the value of a Master in Business Administration (MBA) degree, compared to acquiring your business acumen through various forms of apprenticeship.

The Waning of Business Degrees
Ironically, business schools are facing a tough business problem. The rapid rate of technological change, a booming job market, and the digitization of education are chipping away at the traditional graduate-level business program.

The data speaks for itself.

The Decline of Graduate School Admissions
Enrollment in two-year, full-time MBA programs in the US fell by more than one-third from 2010 to 2016.

While in previous years, top business schools (e.g. Stanford, Harvard, and Wharton) were safe from the decrease in applications, this year, they also felt the waning interest in MBA programs.

Harvard Business School: 4.5 percent decrease in applications, the school’s biggest drop since 2005.
Wharton: 6.7 percent decrease in applications.
Stanford Graduate School: 4.6 percent decrease in applications.

Another signal of change began unfolding over the past week. You may have read news headlines about an emerging college admissions scam, which implicates highly selective US universities, sports coaches, parents, and students in a conspiracy to game the undergraduate admissions process.

Already, students are filing multibillion-dollar civil lawsuits arguing that the scheme has devalued their degrees or denied them a fair admissions opportunity.

MBA Graduates in the Workforce
To meet today’s business needs, startups and massive companies alike are increasingly hiring technologists, developers, and engineers in place of the MBA graduates they may have preferentially hired in the past.

While 85 percent of US employers expect to hire MBA graduates this year (a decrease from 91 percent in 2017), 52 percent of employers worldwide expect to hire graduates with a master’s in data analytics (an increase from 35 percent last year).

We’re also seeing the waning of MBA degree holders at the CEO level.

For decades, an MBA was the hallmark of upward mobility towards the C-suite of top companies.

But as exponential technologies permeate not only products but every part of the supply chain—from manufacturing and shipping to sales, marketing and customer service—that trend is changing by necessity.

Looking at the Harvard Business Review’s Top 100 CEOs in 2018 list, more CEOs on the list held engineering degrees than MBAs (34 held engineering degrees, while 32 held MBAs).

There’s much more to leading innovative companies than an advanced business degree.

How Are Schools Responding?
With disruption to the advanced business education system already here, some business schools are applying notes from their own innovation classes to brace for change.

Over the past half-decade, we’ve seen schools with smaller MBA programs shut their doors in favor of advanced degrees with more specialization. This directly responds to market demand for skills in data science, supply chain, and manufacturing.

Some degrees resemble the precise skills training of technical trades. Others are very much in line with the apprenticeship models we’ll explore next.

Regardless, this new specialization strategy is working and attracting more new students. Over the past decade (2006 to 2016), enrollment in specialized graduate business programs doubled.

Higher education is also seeing a preference shift toward for-profit trade schools, like coding boot camps. This shift is one of several forces pushing universities to adopt skill-specific advanced degrees.

But some schools are slow to adapt, raising the question: how and when will these legacy programs be disrupted? A survey of over 170 business school deans around the world showed that many programs are operating at a loss.

But if these schools are world-class business institutions, as advertised, why do they keep the doors open even while they lose money? The surveyed deans revealed an important insight: they keep the degree program open because of the program’s prestige.

Why Go to Business School?
Shorthand Credibility, Cognitive Biases, and Prestige
Regardless of what knowledge a person takes away from graduate school, attending one of the world’s most rigorous and elite programs gives grads external validation.

With over 55 percent of MBA applicants applying to just 6 percent of graduate business schools, we have a clear cognitive bias toward the perceived elite status of certain universities.

To the outside world, thanks to the power of cognitive biases, an advanced degree is credibility shorthand for your capabilities.

Simply passing through a top school’s filtration system means that you had some level of abilities and merits.

And startup success statistics tend to back up that perceived enhanced capability. Let’s take, for example, universities with the most startup unicorn founders (see the figure below).

When you consider the 320+ unicorn startups around the world today, these numbers become even more impressive. Stanford’s 18 unicorn companies account for over 5 percent of global unicorns, and Harvard is responsible for producing just under 5 percent.

Combined, just these two universities (out of over 5,000 in the US, and thousands more around the world) account for 1 in 10 of the billion-dollar private companies in the world.

By the numbers, the prestigious reputation of these elite business programs has a firm basis in current innovation success.

While prestige may be inherent to the degree earned by graduates from these business programs, the credibility boost from holding one of these degrees is not a guaranteed path to success in the business world.

For example, you might expect that the Harvard School of Business or Stanford Graduate School of Business would come out on top when tallying up the alma maters of Fortune 500 CEOs.

It turns out that the University of Wisconsin-Madison leads the business school pack with 14 CEOs to Harvard’s 12. Beyond prestige, the success these elite business programs see translates directly into cultivating unmatched networks and relationships.

Relationships
Graduate schools—particularly at the upper echelon—are excellent at attracting sharp students.

At an elite business school, if you meet just five to ten people with extraordinary skill sets, personalities, ideas, or networks, then you have returned your $200,000 education investment.

It’s no coincidence that some 40 percent of Silicon Valley venture capitalists are alumni of either Harvard or Stanford.

From future investors to advisors, friends, and potential business partners, relationships are critical to an entrepreneur’s success.

Apprenticeships
As we saw above, graduate business degree programs are melting away in the current wave of exponential change.

With an increasing $1.5 trillion in student debt, there must be a more impactful alternative to attending graduate school for those starting their careers.

When I think about the most important skills I use today as an entrepreneur, writer, and strategic thinker, they didn’t come from my decade of graduate school at Harvard or MIT… they came from my experiences building real technologies and companies, and working with mentors.

Apprenticeship comes in a variety of forms; here, I’ll cover three top-of-mind approaches:

Real-world business acumen via startup accelerators
A direct apprenticeship model
The 6 D’s of mentorship

Startup Accelerators and Business Practicum
Let’s contrast the shrinking interest in MBA programs with applications to a relatively new model of business education: startup accelerators.

Startup accelerators are short-term (typically three to six months), cohort-based programs focusing on providing startup founders with the resources (capital, mentorship, relationships, and education) needed to refine their entrepreneurial acumen.

While graduate business programs have been condensing, startup accelerators are alive, well, and expanding rapidly.

In the 10 years from 2005 (when Paul Graham founded Y Combinator) through 2015, the number of startup accelerators in the US increased by more than tenfold.

The increase in startup accelerator activity hints at a larger trend: our best and brightest business minds are opting to invest their time and efforts in obtaining hands-on experience, creating tangible value for themselves and others, rather than diving into the theory often taught in business school classrooms.

The “Strike Force” Model
The Strike Force is my elite team of young entrepreneurs who work directly with me across all of my companies, travel by my side, sit in on every meeting with me, and help build businesses that change the world.

Previous Strike Force members have gone on to launch successful companies, including Bold Capital Partners, my $250 million venture capital firm.

Strike Force is an apprenticeship for the next generation of exponential entrepreneurs.

To paraphrase my good friend Tony Robbins: If you want to short-circuit the video game, find someone who’s been there and done that and is now doing something you want to one day do.

Every year, over 500,000 apprentices in the US follow this precise template. These apprentices are learning a craft they wish to master, under the mentorship of experts (skilled metal workers, bricklayers, medical technicians, electricians, and more) who have already achieved the desired result.

What if we more readily applied this model to young adults with aspirations of creating massive value through the vehicles of entrepreneurship and innovation?

For the established entrepreneur: How can you bring young entrepreneurs into your organization to create more value for your company, while also passing on your ethos and lessons learned to the next generation?

For the young, driven millennial: How can you find your mentor and convince him or her to take you on as an apprentice? What value can you create for this person in exchange for their guidance and investment in your professional development?

The 6 D’s of Mentorship
In my last blog on education, I shared how mobile device and internet penetration will transform adult literacy and basic education. Mobile phones and connectivity already create extraordinary value for entrepreneurs and young professionals looking to take their business acumen and skill set to the next level.

For all of human history up until the last decade or so, if you wanted to learn from the best and brightest in business, leadership, or strategy, you either needed to search for a dated book that they wrote at the local library or bookstore, or you had to be lucky enough to meet that person for a live conversation.

Now you can access the mentorship of just about any thought leader on the planet, at any time, for free.

Thanks to the power of the internet, mentorship has digitized, demonetized, dematerialized, and democratized.

What do you want to learn about?

Investing? Leadership? Technology? Marketing? Project management?

You can access a near-infinite stream of cutting-edge tools, tactics, and lessons from thousands of top performers from nearly every field—instantaneously, and for free.

For example, every one of Warren Buffett’s letters to his Berkshire Hathaway investors over the past 40 years is available for free on a device that fits in your pocket.

The rise of audio—particularly podcasts and audiobooks—is another underestimated driving force away from traditional graduate business programs and toward apprenticeships.

Over 28 million podcast episodes are available for free. Once you identify the strong signals in the noise, you’re still left with thousands of hours of long-form podcast conversation from which to learn valuable lessons.

Whenever and wherever you want, you can learn from the world’s best. In the future, mentorship and apprenticeship will only become more personalized. Imagine accessing a high-fidelity, AI-powered avatar of Bill Gates, Richard Branson, or Arthur C. Clarke (one of my early mentors) to help guide you through your career.

Virtual mentorship and coaching are powerful education forces that are here to stay.

Bringing It All Together
The education system is rapidly changing. Traditional master’s programs for business are ebbing away in the tides of exponential technologies. Apprenticeship models are reemerging as an effective way to train tomorrow’s leaders.

In a future blog, I’ll revisit the concept of apprenticeships and other effective business school alternatives.

If you are a young, ambitious entrepreneur (or the parent of one), remember that you live in the most abundant time ever in human history to refine your craft.

Right now, you have access to world-class mentorship and cutting-edge best-practices—literally in the palm of your hand. What will you do with this extraordinary power?

Join Me
Abundance-Digital Online Community: I’ve created a Digital/Online community of bold, abundance-minded entrepreneurs called Abundance-Digital. Abundance-Digital is my ‘onramp’ for exponential entrepreneurs – those who want to get involved and play at a higher level. Click here to learn more.

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Posted in Human Robots

#434580 How Genome Sequencing and Senolytics Can ...

The causes of aging are extremely complex and unclear. 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 find practical ways to extend our healthspan.

Here, in Part 2 of a series of blogs on longevity and vitality, I explore how genome sequencing and editing, along with new classes of anti-aging drugs, are augmenting our biology to further extend our healthy lives.

In this blog I’ll cover two classes of emerging technologies:

Genome Sequencing and Editing;
Senolytics, Nutraceuticals & Pharmaceuticals.

Let’s dive in.

Genome Sequencing & 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 to 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 $5,000 in 2012.

Today, the cost of genome sequencing has dropped below $500, 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 blog).
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 from the University of Chicago recently used CRISPR to genetically engineer cocaine resistance into mice.

Researchers at the University of Texas Southwestern Medical Center used CRISPR to reverse the gene defect causing Duchenne muscular dystrophy (DMD) in dogs (DMD is the most common fatal genetic disease in children).

With great power comes great responsibility, and 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.

Setting aside the significant ethical conversations, 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 & 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 Biotechnologiesis pioneering a programmable gene therapy that can destroy cells based on their internal biochemistry.
SIWA Therapeuticsis 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.

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 as 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 started 2018 by going public) 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
A 30.6 percent decrease in respiratory tract infections

Impressive, to say the least.

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.

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 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 blog 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 to 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?

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#434534 To Extend Our Longevity, First We Must ...

Healthcare today is reactive, retrospective, bureaucratic, and expensive. It’s sick care, not healthcare.

But that is radically changing at an exponential rate.

Through this multi-part blog series on longevity, I’ll take a deep dive into aging, longevity, and healthcare technologies that are working together to dramatically extend the human lifespan, disrupting the $3 trillion healthcare system in the process.

I’ll begin the series by explaining the nine hallmarks of aging, as explained in this journal article. Next, I’ll break down the emerging technologies and initiatives working to combat these nine hallmarks. Finally, I’ll explore the transformative implications of dramatically extending the human health span.

In this blog I’ll cover:

Why the healthcare system is broken
Why, despite this, we live in the healthiest time in human history
The nine mechanisms of aging

Let’s dive in.

The System is Broken—Here’s the Data:

Doctors spend $210 billion per year on procedures that aren’t based on patient need, but fear of liability.
Americans spend, on average, $8,915 per person on healthcare—more than any other country on Earth.
Prescription drugs cost around 50 percent more in the US than in other industrialized countries.
At current rates, by 2025, nearly 25 percent of the US GDP will be spent on healthcare.
It takes 12 years and $359 million, on average, to take a new drug from the lab to a patient.
Only 5 in 5,000 of these new drugs proceed to human testing. From there, only 1 of those 5 is actually approved for human use.

And Yet, We Live in the Healthiest Time in Human History
Consider these insights, which I adapted from Max Roser’s excellent database Our World in Data:

Right now, the countries with the lowest life expectancy in the world still have higher life expectancies than the countries with the highest life expectancy did in 1800.
In 1841, a 5-year-old had a life expectancy of 55 years. Today, a 5-year-old can expect to live 82 years—an increase of 27 years.
We’re seeing a dramatic increase in healthspan. In 1845, a newborn would expect to live to 40 years old. For a 70-year-old, that number became 79. Now, people of all ages can expect to live to be 81 to 86 years old.
100 years ago, 1 of 3 children would die before the age of 5. As of 2015, the child mortality rate fell to just 4.3 percent.
The cancer mortality rate has declined 27 percent over the past 25 years.

Figure: Around the globe, life expectancy has doubled since the 1800s. | Image from Life Expectancy by Max Roser – Our World in Data / CC BY SA
Figure: A dramatic reduction in child mortality in 1800 vs. in 2015. | Image from Child Mortality by Max Roser – Our World in Data / CC BY SA
The 9 Mechanisms of Aging
*This section was adapted from CB INSIGHTS: The Future Of Aging.

Longevity, healthcare, and aging are intimately linked.

With better healthcare, we can better treat some of the leading causes of death, impacting how long we live.

By investigating how to treat diseases, we’ll inevitably better understand what causes these diseases in the first place, which directly correlates to why we age.

Following are the nine hallmarks of aging. I’ll share examples of health and longevity technologies addressing each of these later in this blog series.

Genomic instability: As we age, the environment and normal cellular processes cause damage to our genes. Activities like flying at high altitude, for example, expose us to increased radiation or free radicals. This damage compounds over the course of life and is known to accelerate aging.
Telomere attrition: Each strand of DNA in the body (known as chromosomes) is capped by telomeres. These short snippets of DNA repeated thousands of times are designed to protect the bulk of the chromosome. Telomeres shorten as our DNA replicates; if a telomere reaches a certain critical shortness, a cell will stop dividing, resulting in increased incidence of disease.
Epigenetic alterations: Over time, environmental factors will change how genes are expressed, i.e., how certain sequences of DNA are read and the instruction set implemented.
Loss of proteostasis: Over time, different proteins in our body will no longer fold and function as they are supposed to, resulting in diseases ranging from cancer to neurological disorders.
Deregulated nutrient-sensing: Nutrient levels in the body can influence various metabolic pathways. Among the affected parts of these pathways are proteins like IGF-1, mTOR, sirtuins, and AMPK. Changing levels of these proteins’ pathways has implications on longevity.
Mitochondrial dysfunction: Mitochondria (our cellular power plants) begin to decline in performance as we age. Decreased performance results in excess fatigue and other symptoms of chronic illnesses associated with aging.
Cellular senescence: As cells age, they stop dividing and cannot be removed from the body. They build up and typically cause increased inflammation.
Stem cell exhaustion: As we age, our supply of stem cells begins to diminish as much as 100 to 10,000-fold in different tissues and organs. In addition, stem cells undergo genetic mutations, which reduce their quality and effectiveness at renovating and repairing the body.
Altered intercellular communication: The communication mechanisms that cells use are disrupted as cells age, resulting in decreased ability to transmit information between cells.

Conclusion
Over the past 200 years, we have seen an abundance of healthcare technologies enable a massive lifespan boom.

Now, exponential technologies like artificial intelligence, 3D printing and sensors, as well as tremendous advancements in genomics, stem cell research, chemistry, and many other fields, are beginning to tackle the fundamental issues of why we age.

In the next blog in this series, we will dive into how genome sequencing and editing, along with new classes of drugs, are augmenting our biology to further extend our healthy lives.

What will you be able to achieve with an extra 30 to 50 healthy years (or longer) in your lifespan? Personally, I’m excited for a near-infinite lifespan to take on moonshots.

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