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#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

#434803 Is AI as Smart as a Mouse? A Crow? An ...

Companies are deploying artificial intelligence systems but don’t know if they'll measure up 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?

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#434781 What Would It Mean for AI to Become ...

As artificial intelligence systems take on more tasks and solve more problems, it’s hard to say which is rising faster: our interest in them or our fear of them. Futurist Ray Kurzweil famously predicted that “By 2029, computers will have emotional intelligence and be convincing as people.”

We don’t know how accurate this prediction will turn out to be. Even if it takes more than 10 years, though, is it really possible for machines to become conscious? If the machines Kurzweil describes say they’re conscious, does that mean they actually are?

Perhaps a more relevant question at this juncture is: what is consciousness, and how do we replicate it if we don’t understand it?

In a panel discussion at South By Southwest titled “How AI Will Design the Human Future,” experts from academia and industry discussed these questions and more.

Wait, What Is AI?
Most of AI’s recent feats—diagnosing illnesses, participating in debate, writing realistic text—involve machine learning, which uses statistics to find patterns in large datasets then uses those patterns to make predictions. However, “AI” has been used to refer to everything from basic software automation and algorithms to advanced machine learning and deep learning.

“The term ‘artificial intelligence’ is thrown around constantly and often incorrectly,” said Jennifer Strong, a reporter at the Wall Street Journal and host of the podcast “The Future of Everything.” Indeed, one study found that 40 percent of European companies that claim to be working on or using AI don’t actually use it at all.

Dr. Peter Stone, associate chair of computer science at UT Austin, was the study panel chair on the 2016 One Hundred Year Study on Artificial Intelligence (or AI100) report. Based out of Stanford University, AI100 is studying and anticipating how AI will impact our work, our cities, and our lives.

“One of the first things we had to do was define AI,” Stone said. They defined it as a collection of different technologies inspired by the human brain to be able to perceive their surrounding environment and figure out what actions to take given these inputs.

Modeling on the Unknown
Here’s the crazy thing about that definition (and about AI itself): we’re essentially trying to re-create the abilities of the human brain without having anything close to a thorough understanding of how the human brain works.

“We’re starting to pair our brains with computers, but brains don’t understand computers and computers don’t understand brains,” Stone said. Dr. Heather Berlin, cognitive neuroscientist and professor of psychiatry at the Icahn School of Medicine at Mount Sinai, agreed. “It’s still one of the greatest mysteries how this three-pound piece of matter can give us all our subjective experiences, thoughts, and emotions,” she said.

This isn’t to say we’re not making progress; there have been significant neuroscience breakthroughs in recent years. “This has been the stuff of science fiction for a long time, but now there’s active work being done in this area,” said Amir Husain, CEO and founder of Austin-based AI company Spark Cognition.

Advances in brain-machine interfaces show just how much more we understand the brain now than we did even a few years ago. Neural implants are being used to restore communication or movement capabilities in people who’ve been impaired by injury or illness. Scientists have been able to transfer signals from the brain to prosthetic limbs and stimulate specific circuits in the brain to treat conditions like Parkinson’s, PTSD, and depression.

But much of the brain’s inner workings remain a deep, dark mystery—one that will have to be further solved if we’re ever to get from narrow AI, which refers to systems that can perform specific tasks and is where the technology stands today, to artificial general intelligence, or systems that possess the same intelligence level and learning capabilities as humans.

The biggest question that arises here, and one that’s become a popular theme across stories and films, is if machines achieve human-level general intelligence, does that also mean they’d be conscious?

Wait, What Is Consciousness?
As valuable as the knowledge we’ve accumulated about the brain is, it seems like nothing more than a collection of disparate facts when we try to put it all together to understand consciousness.

“If you can replace one neuron with a silicon chip that can do the same function, then replace another neuron, and another—at what point are you still you?” Berlin asked. “These systems will be able to pass the Turing test, so we’re going to need another concept of how to measure consciousness.”

Is consciousness a measurable phenomenon, though? Rather than progressing by degrees or moving through some gray area, isn’t it pretty black and white—a being is either conscious or it isn’t?

This may be an outmoded way of thinking, according to Berlin. “It used to be that only philosophers could study consciousness, but now we can study it from a scientific perspective,” she said. “We can measure changes in neural pathways. It’s subjective, but depends on reportability.”

She described three levels of consciousness: pure subjective experience (“Look, the sky is blue”), awareness of one’s own subjective experience (“Oh, it’s me that’s seeing the blue sky”), and relating one subjective experience to another (“The blue sky reminds me of a blue ocean”).

“These subjective states exist all the way down the animal kingdom. As humans we have a sense of self that gives us another depth to that experience, but it’s not necessary for pure sensation,” Berlin said.

Husain took this definition a few steps farther. “It’s this self-awareness, this idea that I exist separate from everything else and that I can model myself,” he said. “Human brains have a wonderful simulator. They can propose a course of action virtually, in their minds, and see how things play out. The ability to include yourself as an actor means you’re running a computation on the idea of yourself.”

Most of the decisions we make involve envisioning different outcomes, thinking about how each outcome would affect us, and choosing which outcome we’d most prefer.

“Complex tasks you want to achieve in the world are tied to your ability to foresee the future, at least based on some mental model,” Husain said. “With that view, I as an AI practitioner don’t see a problem implementing that type of consciousness.”

Moving Forward Cautiously (But Not too Cautiously)
To be clear, we’re nowhere near machines achieving artificial general intelligence or consciousness, and whether a “conscious machine” is possible—not to mention necessary or desirable—is still very much up for debate.

As machine intelligence continues to advance, though, we’ll need to walk the line between progress and risk management carefully.

Improving the transparency and explainability of AI systems is one crucial goal AI developers and researchers are zeroing in on. Especially in applications that could mean the difference between life and death, AI shouldn’t advance without people being able to trace how it’s making decisions and reaching conclusions.

Medicine is a prime example. “There are already advances that could save lives, but they’re not being used because they’re not trusted by doctors and nurses,” said Stone. “We need to make sure there’s transparency.” Demanding too much transparency would also be a mistake, though, because it will hinder the development of systems that could at best save lives and at worst improve efficiency and free up doctors to have more face time with patients.

Similarly, self-driving cars have great potential to reduce deaths from traffic fatalities. But even though humans cause thousands of deadly crashes every day, we’re terrified by the idea of self-driving cars that are anything less than perfect. “If we only accept autonomous cars when there’s zero probability of an accident, then we will never accept them,” Stone said. “Yet we give 16-year-olds the chance to take a road test with no idea what’s going on in their brains.”

This brings us back to the fact that, in building tech modeled after the human brain—which has evolved over millions of years—we’re working towards an end whose means we don’t fully comprehend, be it something as basic as choosing when to brake or accelerate or something as complex as measuring consciousness.

“We shouldn’t charge ahead and do things just because we can,” Stone said. “The technology can be very powerful, which is exciting, but we have to consider its implications.”

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#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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