Tag Archives: 2018

#434823 The Tangled Web of Turning Spider Silk ...

Spider-Man is one of the most popular superheroes of all time. It’s a bit surprising given that one of the more common phobias is arachnophobia—a debilitating fear of spiders.

Perhaps more fantastical is that young Peter Parker, a brainy high school science nerd, seemingly developed overnight the famous web-shooters and the synthetic spider silk that he uses to swing across the cityscape like Tarzan through the jungle.

That’s because scientists have been trying for decades to replicate spider silk, a material that is five times stronger than steel, among its many superpowers. In recent years, researchers have been untangling the protein-based fiber’s structure down to the molecular level, leading to new insights and new potential for eventual commercial uses.

The applications for such a material seem near endless. There’s the more futuristic visions, like enabling robotic “muscles” for human-like movement or ensnaring real-life villains with a Spider-Man-like web. Near-term applications could include the biomedical industry, such as bandages and adhesives, and as a replacement textile for everything from rope to seat belts to parachutes.

Spinning Synthetic Spider Silk
Randy Lewis has been studying the properties of spider silk and developing methods for producing it synthetically for more than three decades. In the 1990s, his research team was behind cloning the first spider silk gene, as well as the first to identify and sequence the proteins that make up the six different silks that web slingers make. Each has different mechanical properties.

“So our thought process was that you could take that information and begin to to understand what made them strong and what makes them stretchy, and why some are are very stretchy and some are not stretchy at all, and some are stronger and some are weaker,” explained Lewis, a biology professor at Utah State University and director of the Synthetic Spider Silk Lab, in an interview with Singularity Hub.

Spiders are naturally territorial and cannibalistic, so any intention to farm silk naturally would likely end in an orgy of arachnid violence. Instead, Lewis and company have genetically modified different organisms to produce spider silk synthetically, including inserting a couple of web-making genes into the genetic code of goats. The goats’ milk contains spider silk proteins.

The lab also produces synthetic spider silk through a fermentation process not entirely dissimilar to brewing beer, but using genetically modified bacteria to make the desired spider silk proteins. A similar technique has been used for years to make a key enzyme in cheese production. More recently, companies are using transgenic bacteria to make meat and milk proteins, entirely bypassing animals in the process.

The same fermentation technology is used by a chic startup called Bolt Threads outside of San Francisco that has raised more than $200 million for fashionable fibers made out of synthetic spider silk it calls Microsilk. (The company is also developing a second leather-like material, Mylo, using the underground root structure of mushrooms known as mycelium.)

Lewis’ lab also uses transgenic silkworms to produce a kind of composite material made up of the domesticated insect’s own silk proteins and those of spider silk. “Those have some fairly impressive properties,” Lewis said.

The researchers are even experimenting with genetically modified alfalfa. One of the big advantages there is that once the spider silk protein has been extracted, the remaining protein could be sold as livestock feed. “That would bring the cost of spider silk protein production down significantly,” Lewis said.

Building a Better Web
Producing synthetic spider silk isn’t the problem, according to Lewis, but the ability to do it at scale commercially remains a sticking point.

Another challenge is “weaving” the synthetic spider silk into usable products that can take advantage of the material’s marvelous properties.

“It is possible to make silk proteins synthetically, but it is very hard to assemble the individual proteins into a fiber or other material forms,” said Markus Buehler, head of the Department of Civil and Environmental Engineering at MIT, in an email to Singularity Hub. “The spider has a complex spinning duct in which silk proteins are exposed to physical forces, chemical gradients, the combination of which generates the assembly of molecules that leads to silk fibers.”

Buehler recently co-authored a paper in the journal Science Advances that found dragline spider silk exhibits different properties in response to changes in humidity that could eventually have applications in robotics.

Specifically, spider silk suddenly contracts and twists above a certain level of relative humidity, exerting enough force to “potentially be competitive with other materials being explored as actuators—devices that move to perform some activity such as controlling a valve,” according to a press release.

Studying Spider Silk Up Close
Recent studies at the molecular level are helping scientists learn more about the unique properties of spider silk, which may help researchers develop materials with extraordinary capabilities.

For example, scientists at Arizona State University used magnetic resonance tools and other instruments to image the abdomen of a black widow spider. They produced what they called the first molecular-level model of spider silk protein fiber formation, providing insights on the nanoparticle structure. The research was published last October in Proceedings of the National Academy of Sciences.

A cross section of the abdomen of a black widow (Latrodectus Hesperus) spider used in this study at Arizona State University. Image Credit: Samrat Amin.
Also in 2018, a study presented in Nature Communications described a sort of molecular clamp that binds the silk protein building blocks, which are called spidroins. The researchers observed for the first time that the clamp self-assembles in a two-step process, contributing to the extensibility, or stretchiness, of spider silk.

Another team put the spider silk of a brown recluse under an atomic force microscope, discovering that each strand, already 1,000 times thinner than a human hair, is made up of thousands of nanostrands. That helps explain its extraordinary tensile strength, though technique is also a factor, as the brown recluse uses a special looping method to reinforce its silk strands. The study also appeared last year in the journal ACS Macro Letters.

Making Spider Silk Stick
Buehler said his team is now trying to develop better and faster predictive methods to design silk proteins using artificial intelligence.

“These new methods allow us to generate new protein designs that do not naturally exist and which can be explored to optimize certain desirable properties like torsional actuation, strength, bioactivity—for example, tissue engineering—and others,” he said.

Meanwhile, Lewis’ lab has discovered a method that allows it to solubilize spider silk protein in what is essentially a water-based solution, eschewing acids or other toxic compounds that are normally used in the process.

That enables the researchers to develop materials beyond fiber, including adhesives that “are better than an awful lot of the current commercial adhesives,” Lewis said, as well as coatings that could be used to dampen vibrations, for example.

“We’re making gels for various kinds of of tissue regeneration, as well as drug delivery, and things like that,” he added. “So we’ve expanded the use profile from something beyond fibers to something that is a much more extensive portfolio of possible kinds of materials.”

And, yes, there’s even designs at the Synthetic Spider Silk Lab for developing a Spider-Man web-slinger material. The US Navy is interested in non-destructive ways of disabling an enemy vessel, such as fouling its propeller. The project also includes producing synthetic proteins from the hagfish, an eel-like critter that exudes a gelatinous slime when threatened.

Lewis said that while the potential for spider silk is certainly headline-grabbing, he cautioned that much of the hype is not focused on the unique mechanical properties that could lead to advances in healthcare and other industries.

“We want to see spider silk out there because it’s a unique material, not because it’s got marketing appeal,” he said.

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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

#434759 To Be Ethical, AI Must Become ...

As over-hyped as artificial intelligence is—everyone’s talking about it, few fully understand it, it might leave us all unemployed but also solve all the world’s problems—its list of accomplishments is growing. AI can now write realistic-sounding text, give a debating champ a run for his money, diagnose illnesses, and generate fake human faces—among much more.

After training these systems on massive datasets, their creators essentially just let them do their thing to arrive at certain conclusions or outcomes. The problem is that more often than not, even the creators don’t know exactly why they’ve arrived at those conclusions or outcomes. There’s no easy way to trace a machine learning system’s rationale, so to speak. The further we let AI go down this opaque path, the more likely we are to end up somewhere we don’t want to be—and may not be able to come back from.

In a panel at the South by Southwest interactive festival last week titled “Ethics and AI: How to plan for the unpredictable,” experts in the field shared their thoughts on building more transparent, explainable, and accountable AI systems.

Not New, but Different
Ryan Welsh, founder and director of explainable AI startup Kyndi, pointed out that having knowledge-based systems perform advanced tasks isn’t new; he cited logistical, scheduling, and tax software as examples. What’s new is the learning component, our inability to trace how that learning occurs, and the ethical implications that could result.

“Now we have these systems that are learning from data, and we’re trying to understand why they’re arriving at certain outcomes,” Welsh said. “We’ve never actually had this broad society discussion about ethics in those scenarios.”

Rather than continuing to build AIs with opaque inner workings, engineers must start focusing on explainability, which Welsh broke down into three subcategories. Transparency and interpretability come first, and refer to being able to find the units of high influence in a machine learning network, as well as the weights of those units and how they map to specific data and outputs.

Then there’s provenance: knowing where something comes from. In an ideal scenario, for example, Open AI’s new text generator would be able to generate citations in its text that reference academic (and human-created) papers or studies.

Explainability itself is the highest and final bar and refers to a system’s ability to explain itself in natural language to the average user by being able to say, “I generated this output because x, y, z.”

“Humans are unique in our ability and our desire to ask why,” said Josh Marcuse, executive director of the Defense Innovation Board, which advises Department of Defense senior leaders on innovation. “The reason we want explanations from people is so we can understand their belief system and see if we agree with it and want to continue to work with them.”

Similarly, we need to have the ability to interrogate AIs.

Two Types of Thinking
Welsh explained that one big barrier standing in the way of explainability is the tension between the deep learning community and the symbolic AI community, which see themselves as two different paradigms and historically haven’t collaborated much.

Symbolic or classical AI focuses on concepts and rules, while deep learning is centered around perceptions. In human thought this is the difference between, for example, deciding to pass a soccer ball to a teammate who is open (you make the decision because conceptually you know that only open players can receive passes), and registering that the ball is at your feet when someone else passes it to you (you’re taking in information without making a decision about it).

“Symbolic AI has abstractions and representation based on logic that’s more humanly comprehensible,” Welsh said. To truly mimic human thinking, AI needs to be able to both perceive information and conceptualize it. An example of perception (deep learning) in an AI is recognizing numbers within an image, while conceptualization (symbolic learning) would give those numbers a hierarchical order and extract rules from the hierachy (4 is greater than 3, and 5 is greater than 4, therefore 5 is also greater than 3).

Explainability comes in when the system can say, “I saw a, b, and c, and based on that decided x, y, or z.” DeepMind and others have recently published papers emphasizing the need to fuse the two paradigms together.

Implications Across Industries
One of the most prominent fields where AI ethics will come into play, and where the transparency and accountability of AI systems will be crucial, is defense. Marcuse said, “We’re accountable beings, and we’re responsible for the choices we make. Bringing in tech or AI to a battlefield doesn’t strip away that meaning and accountability.”

In fact, he added, rather than worrying about how AI might degrade human values, people should be asking how the tech could be used to help us make better moral choices.

It’s also important not to conflate AI with autonomy—a worst-case scenario that springs to mind is an intelligent destructive machine on a rampage. But in fact, Marcuse said, in the defense space, “We have autonomous systems today that don’t rely on AI, and most of the AI systems we’re contemplating won’t be autonomous.”

The US Department of Defense released its 2018 artificial intelligence strategy last month. It includes developing a robust and transparent set of principles for defense AI, investing in research and development for AI that’s reliable and secure, continuing to fund research in explainability, advocating for a global set of military AI guidelines, and finding ways to use AI to reduce the risk of civilian casualties and other collateral damage.

Though these were designed with defense-specific aims in mind, Marcuse said, their implications extend across industries. “The defense community thinks of their problems as being unique, that no one deals with the stakes and complexity we deal with. That’s just wrong,” he said. Making high-stakes decisions with technology is widespread; safety-critical systems are key to aviation, medicine, and self-driving cars, to name a few.

Marcuse believes the Department of Defense can invest in AI safety in a way that has far-reaching benefits. “We all depend on technology to keep us alive and safe, and no one wants machines to harm us,” he said.

A Creation Superior to Its Creator
That said, we’ve come to expect technology to meet our needs in just the way we want, all the time—servers must never be down, GPS had better not take us on a longer route, Google must always produce the answer we’re looking for.

With AI, though, our expectations of perfection may be less reasonable.

“Right now we’re holding machines to superhuman standards,” Marcuse said. “We expect them to be perfect and infallible.” Take self-driving cars. They’re conceived of, built by, and programmed by people, and people as a whole generally aren’t great drivers—just look at traffic accident death rates to confirm that. But the few times self-driving cars have had fatal accidents, there’s been an ensuing uproar and backlash against the industry, as well as talk of implementing more restrictive regulations.

This can be extrapolated to ethics more generally. We as humans have the ability to explain our decisions, but many of us aren’t very good at doing so. As Marcuse put it, “People are emotional, they confabulate, they lie, they’re full of unconscious motivations. They don’t pass the explainability test.”

Why, then, should explainability be the standard for AI?

Even if humans aren’t good at explaining our choices, at least we can try, and we can answer questions that probe at our decision-making process. A deep learning system can’t do this yet, so working towards being able to identify which input data the systems are triggering on to make decisions—even if the decisions and the process aren’t perfect—is the direction we need to head.

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#434673 The World’s Most Valuable AI ...

It recognizes our faces. It knows the videos we might like. And it can even, perhaps, recommend the best course of action to take to maximize our personal health.

Artificial intelligence and its subset of disciplines—such as machine learning, natural language processing, and computer vision—are seemingly becoming integrated into our daily lives whether we like it or not. What was once sci-fi is now ubiquitous research and development in company and university labs around the world.

Similarly, the startups working on many of these AI technologies have seen their proverbial stock rise. More than 30 of these companies are now valued at over a billion dollars, according to data research firm CB Insights, which itself employs algorithms to provide insights into the tech business world.

Private companies with a billion-dollar valuation were so uncommon not that long ago that they were dubbed unicorns. Now there are 325 of these once-rare creatures, with a combined valuation north of a trillion dollars, as CB Insights maintains a running count of this exclusive Unicorn Club.

The subset of AI startups accounts for about 10 percent of the total membership, growing rapidly in just 4 years from 0 to 32. Last year, an unprecedented 17 AI startups broke the billion-dollar barrier, with 2018 also a record year for venture capital into private US AI companies at $9.3 billion, CB Insights reported.

What exactly is all this money funding?

AI Keeps an Eye Out for You
Let’s start with the bad news first.

Facial recognition is probably one of the most ubiquitous applications of AI today. It’s actually a decades-old technology often credited to a man named Woodrow Bledsoe, who used an instrument called a RAND tablet that could semi-autonomously match faces from a database. That was in the 1960s.

Today, most of us are familiar with facial recognition as a way to unlock our smartphones. But the technology has gained notoriety as a surveillance tool of law enforcement, particularly in China.

It’s no secret that the facial recognition algorithms developed by several of the AI unicorns from China—SenseTime, CloudWalk, and Face++ (also known as Megvii)—are used to monitor the country’s 1.3 billion citizens. Police there are even equipped with AI-powered eyeglasses for such purposes.

A fourth billion-dollar Chinese startup, Yitu Technologies, also produces a platform for facial recognition in the security realm, and develops AI systems in healthcare on top of that. For example, its CARE.AITM Intelligent 4D Imaging System for Chest CT can reputedly identify in real time a variety of lesions for the possible early detection of cancer.

The AI Doctor Is In
As Peter Diamandis recently noted, AI is rapidly augmenting healthcare and longevity. He mentioned another AI unicorn from China in this regard—iCarbonX, which plans to use machines to develop personalized health plans for every individual.

A couple of AI unicorns on the hardware side of healthcare are OrCam Technologies and Butterfly. The former, an Israeli company, has developed a wearable device for the vision impaired called MyEye that attaches to one’s eyeglasses. The device can identify people and products, as well as read text, conveying the information through discrete audio.

Butterfly Network, out of Connecticut, has completely upended the healthcare market with a handheld ultrasound machine that works with a smartphone.

“Orcam and Butterfly are amazing examples of how machine learning can be integrated into solutions that provide a step-function improvement over state of the art in ultra-competitive markets,” noted Andrew Byrnes, investment director at Comet Labs, a venture capital firm focused on AI and robotics, in an email exchange with Singularity Hub.

AI in the Driver’s Seat
Comet Labs’ portfolio includes two AI unicorns, Megvii and Pony.ai.

The latter is one of three billion-dollar startups developing the AI technology behind self-driving cars, with the other two being Momenta.ai and Zoox.

Founded in 2016 near San Francisco (with another headquarters in China), Pony.ai debuted its latest self-driving system, called PonyAlpha, last year. The platform uses multiple sensors (LiDAR, cameras, and radar) to navigate its environment, but its “sensor fusion technology” makes things simple by choosing the most reliable sensor data for any given driving scenario.

Zoox is another San Francisco area startup founded a couple of years earlier. In late 2018, it got the green light from the state of California to be the first autonomous vehicle company to transport a passenger as part of a pilot program. Meanwhile, China-based Momenta.ai is testing level four autonomy for its self-driving system. Autonomous driving levels are ranked zero to five, with level five being equal to a human behind the wheel.

The hype around autonomous driving is currently in overdrive, and Byrnes thinks regulatory roadblocks will keep most self-driving cars in idle for the foreseeable future. The exception, he said, is China, which is adopting a “systems” approach to autonomy for passenger transport.

“If [autonomous mobility] solves bigger problems like traffic that can elicit government backing, then that has the potential to go big fast,” he said. “This is why we believe Pony.ai will be a winner in the space.”

AI in the Back Office
An AI-powered technology that perhaps only fans of the cult classic Office Space might appreciate has suddenly taken the business world by storm—robotic process automation (RPA).

RPA companies take the mundane back office work, such as filling out invoices or processing insurance claims, and turn it over to bots. The intelligent part comes into play because these bots can tackle unstructured data, such as text in an email or even video and pictures, in order to accomplish an increasing variety of tasks.

Both Automation Anywhere and UiPath are older companies, founded in 2003 and 2005, respectively. However, since just 2017, they have raised nearly a combined $1 billion in disclosed capital.

Cybersecurity Embraces AI
Cybersecurity is another industry where AI is driving investment into startups. Sporting imposing names like CrowdStrike, Darktrace, and Tanium, these cybersecurity companies employ different machine-learning techniques to protect computers and other IT assets beyond the latest software update or virus scan.

Darktrace, for instance, takes its inspiration from the human immune system. Its algorithms can purportedly “learn” the unique pattern of each device and user on a network, detecting emerging problems before things spin out of control.

All three companies are used by major corporations and governments around the world. CrowdStrike itself made headlines a few years ago when it linked the hacking of the Democratic National Committee email servers to the Russian government.

Looking Forward
I could go on, and introduce you to the world’s most valuable startup, a Chinese company called Bytedance that is valued at $75 billion for news curation and an app to create 15-second viral videos. But that’s probably not where VC firms like Comet Labs are generally putting their money.

Byrnes sees real value in startups that are taking “data-driven approaches to problems specific to unique industries.” Take the example of Chicago-based unicorn Uptake Technologies, which analyzes incoming data from machines, from wind turbines to tractors, to predict problems before they occur with the machinery. A not-yet unicorn called PingThings in the Comet Labs portfolio does similar predictive analytics for the energy utilities sector.

“One question we like asking is, ‘What does the state of the art look like in your industry in three to five years?’” Byrnes said. “We ask that a lot, then we go out and find the technology-focused teams building those things.”

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