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#434580 How Genome Sequencing and Senolytics Can ...

The causes of aging are extremely complex and unclear. With the dramatic demonetization of genome reading and editing over the past decade, and Big Pharma, startups, and the FDA starting to face aging as a disease, we are starting to find practical ways to extend our healthspan.

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

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

Genome Sequencing and Editing;
Senolytics, Nutraceuticals & Pharmaceuticals.

Let’s dive in.

Genome Sequencing & Editing
Your genome is the software that runs your body.

A sequence of 3.2 billion letters makes you “you.” These base pairs of A’s, T’s, C’s, and G’s determine your hair color, your height, your personality, your propensity to disease, your lifespan, and so on.

Until recently, it’s been very difficult to rapidly and cheaply “read” these letters—and even more difficult to understand what they mean.

Since 2001, the cost to sequence a whole human genome has plummeted exponentially, outpacing Moore’s Law threefold. From an initial cost of $3.7 billion, it dropped to $10 million in 2006, and to $5,000 in 2012.

Today, the cost of genome sequencing has dropped below $500, and according to Illumina, the world’s leading sequencing company, the process will soon cost about $100 and take about an hour to complete.

This represents one of the most powerful and transformative technology revolutions in healthcare.

When we understand your genome, we’ll be able to understand how to optimize “you.”

We’ll know the perfect foods, the perfect drugs, the perfect exercise regimen, and the perfect supplements, just for you.
We’ll understand what microbiome types, or gut flora, are ideal for you (more on this in a later blog).
We’ll accurately predict how specific sedatives and medicines will impact you.
We’ll learn which diseases and illnesses you’re most likely to develop and, more importantly, how to best prevent them from developing in the first place (rather than trying to cure them after the fact).

CRISPR Gene Editing
In addition to reading the human genome, scientists can now edit a genome using a naturally-occurring biological system discovered in 1987 called CRISPR/Cas9.

Short for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9, the editing system was adapted from a naturally-occurring defense system found in bacteria.

Here’s how it works:

The bacteria capture snippets of DNA from invading viruses (or bacteriophage) and use them to create DNA segments known as CRISPR arrays.
The CRISPR arrays allow the bacteria to “remember” the viruses (or closely related ones), and defend against future invasions.
If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses’ DNA. The bacteria then use Cas9 to cut the DNA apart, which disables the virus.

Most importantly, CRISPR is cheap, quick, easy to use, and more accurate than all previous gene editing methods. As a result, CRISPR/Cas9 has swept through labs around the world as the way to edit a genome.

A short search in the literature will show an exponential rise in the number of CRISPR-related publications and patents.

2018: Filled With CRISPR Breakthroughs
Early results are impressive. Researchers from the University of Chicago recently used CRISPR to genetically engineer cocaine resistance into mice.

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

With great power comes great responsibility, and moral and ethical dilemmas.

In 2015, Chinese scientists sparked global controversy when they first edited human embryo cells in the lab with the goal of modifying genes that would make the child resistant to smallpox, HIV, and cholera.

Three years later, in November 2018, researcher He Jiankui informed the world that the first set of CRISPR-engineered female twins had been delivered.

To accomplish his goal, Jiankui deleted a region of a receptor on the surface of white blood cells known as CCR5, introducing a rare, natural genetic variation that makes it more difficult for HIV to infect its favorite target, white blood cells.

Setting aside the significant ethical conversations, CRISPR will soon provide us the tools to eliminate diseases, create hardier offspring, produce new environmentally resistant crops, and even wipe out pathogens.

Senolytics, Nutraceuticals & Pharmaceuticals
Over the arc of your life, the cells in your body divide until they reach what is known as the Hayflick limit, or the number of times a normal human cell population will divide before cell division stops, which is typically about 50 divisions.

What normally follows next is programmed cell death or destruction by the immune system. A very small fraction of cells, however, become senescent cells and evade this fate to linger indefinitely.

These lingering cells secrete a potent mix of molecules that triggers chronic inflammation, damages the surrounding tissue structures, and changes the behavior of nearby cells for the worse.

Senescent cells appear to be one of the root causes of aging, causing everything from fibrosis and blood vessel calcification, to localized inflammatory conditions such as osteoarthritis, to diminished lung function.

Fortunately, both the scientific and entrepreneurial communities have begun to work on senolytic therapies, moving the technology for selectively destroying senescent cells out of the laboratory and into a half-dozen startup companies.

Prominent companies in the field include the following:

Unity Biotechnology is developing senolytic medicines to selectively eliminate senescent cells with an initial focus on delivering localized therapy in osteoarthritis, ophthalmology and pulmonary disease.
Oisin Biotechnologiesis pioneering a programmable gene therapy that can destroy cells based on their internal biochemistry.
SIWA Therapeuticsis working on an immunotherapy approach to the problem of senescent cells.

In recent years, researchers have identified or designed a handful of senolytic compounds that can curb aging by regulating senescent cells. Two of these drugs that have gained mainstay research traction are rapamycin and metformin.

Rapamycin
Originally extracted from bacteria found on Easter Island, Rapamycin acts on the m-TOR (mechanistic target of rapamycin) pathway to selectively block a key protein that facilitates cell division.

Currently, rapamycin derivatives are widely used as immunosuppression in organ and bone marrow transplants. Research now suggests that use results in prolonged lifespan and enhanced cognitive and immune function.

PureTech Health subsidiary resTORbio (which started 2018 by going public) is working on a rapamycin-based drug intended to enhance immunity and reduce infection. Their clinical-stage RTB101 drug works by inhibiting part of the mTOR pathway.

Results of the drug’s recent clinical trial include:

Decreased incidence of infection
Improved influenza vaccination response
A 30.6 percent decrease in respiratory tract infections

Impressive, to say the least.

Metformin
Metformin is a widely-used generic drug for mitigating liver sugar production in Type 2 diabetes patients.

Researchers have found that Metformin also reduces oxidative stress and inflammation, which otherwise increase as we age.

There is strong evidence that Metformin can augment cellular regeneration and dramatically mitigate cellular senescence by reducing both oxidative stress and inflammation.

Over 100 studies registered on ClinicalTrials.gov are currently following up on strong evidence of Metformin’s protective effect against cancer.

Nutraceuticals and NAD+
Beyond cellular senescence, certain critical nutrients and proteins tend to decline as a function of age. Nutraceuticals combat aging by supplementing and replenishing these declining nutrient levels.

NAD+ exists in every cell, participating in every process from DNA repair to creating the energy vital for cellular processes. It’s been shown that NAD+ levels decline as we age.

The Elysium Health Basis supplement aims to elevate NAD+ levels in the body to extend one’s lifespan. Elysium’s clinical study reports that Basis increases NAD+ levels consistently by a sustained 40 percent.

Conclusion
These are just a taste of the tremendous momentum that longevity and aging technology has right now. As artificial intelligence and quantum computing transform how we decode our DNA and how we discover drugs, genetics and pharmaceuticals will become truly personalized.

The next blog in this series will demonstrate how artificial intelligence is converging with genetics and pharmaceuticals to transform how we approach longevity, aging, and vitality.

We are edging closer to a dramatically extended healthspan—where 100 is the new 60. What will you create, where will you explore, and how will you spend your time if you are able to add an additional 40 healthy years to your life?

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

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

But that is radically changing at an exponential rate.

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

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

In this blog I’ll cover:

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

Let’s dive in.

The System is Broken—Here’s the Data:

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

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

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

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

Longevity, healthcare, and aging are intimately linked.

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

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

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

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

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

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

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

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

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#432646 How Fukushima Changed Japanese Robotics ...

In March 2011, Japan was hit by a catastrophic earthquake that triggered a terrible tsunami. Thousands were killed and billions of dollars of damage was done in one of the worst disasters of modern times. For a few perilous weeks, though, the eyes of the world were focused on the Fukushima Daiichi nuclear power plant. Its safety systems were unable to cope with the tsunami damage, and there were widespread fears of another catastrophic meltdown that could spread radiation over several countries, like the Chernobyl disaster in the 1980s. A heroic effort that included dumping seawater into the reactor core prevented an even bigger catastrophe. As it is, a hundred thousand people are still evacuated from the area, and it will likely take many years and hundreds of billions of dollars before the region is safe.

Because radiation is so dangerous to humans, the natural solution to the Fukushima disaster was to send in robots to monitor levels of radiation and attempt to begin the clean-up process. The techno-optimists in Japan had discovered a challenge, deep in the heart of that reactor core, that even their optimism could not solve. The radiation fried the circuits of the robots that were sent in, even those specifically designed and built to deal with the Fukushima catastrophe. The power plant slowly became a vast robot graveyard. While some robots initially saw success in measuring radiation levels around the plant—and, recently, a robot was able to identify the melted uranium fuel at the heart of the disaster—hopes of them playing a substantial role in the clean-up are starting to diminish.



In Tokyo’s neon Shibuya district, it can sometimes seem like it’s brighter at night than it is during the daytime. In karaoke booths on the twelfth floor—because everything is on the twelfth floor—overlooking the brightly-lit streets, businessmen unwind by blasting out pop hits. It can feel like the most artificial place on Earth; your senses are dazzled by the futuristic techno-optimism. Stock footage of the area has become symbolic of futurism and modernity.

Japan has had a reputation for being a nation of futurists for a long time. We’ve already described how tech giant Softbank, headed by visionary founder Masayoshi Son, is investing billions in a technological future, including plans for the world’s largest solar farm.

When Google sold pioneering robotics company Boston Dynamics in 2017, Softbank added it to their portfolio, alongside the famous Nao and Pepper robots. Some may think that Son is taking a gamble in pursuing a robotics project even Google couldn’t succeed in, but this is a man who lost nearly everything in the dot-com crash of 2000. The fact that even this reversal didn’t dent his optimism and faith in technology is telling. But how long can it last?

The failure of Japan’s robots to deal with the immense challenge of Fukushima has sparked something of a crisis of conscience within the industry. Disaster response is an obvious stepping-stone technology for robots. Initially, producing a humanoid robot will be very costly, and the robot will be less capable than a human; building a robot to wait tables might not be particularly economical yet. Building a robot to do jobs that are too dangerous for humans is far more viable. Yet, at Fukushima, in one of the most advanced nations in the world, many of the robots weren’t up to the task.

Nowhere was this crisis more felt than Honda; the company had developed ASIMO, which stunned the world in 2000 and continues to fascinate as an iconic humanoid robot. Despite all this technological advancement, however, Honda knew that ASIMO was still too unreliable for the real world.

It was Fukushima that triggered a sea-change in Honda’s approach to robotics. Two years after the disaster, there were rumblings that Honda was developing a disaster robot, and in October 2017, the prototype was revealed to the public for the first time. It’s not yet ready for deployment in disaster zones, however. Interestingly, the creators chose not to give it dexterous hands but instead to assume that remotely-operated tools fitted to the robot would be a better solution for the range of circumstances it might encounter.

This shift in focus for humanoid robots away from entertainment and amusement like ASIMO, and towards being practically useful, has been mirrored across the world.

In 2015, also inspired by the Fukushima disaster and the lack of disaster-ready robots, the DARPA Robotics Challenge tested humanoid robots with a range of tasks that might be needed in emergency response, such as driving cars, opening doors, and climbing stairs. The Terminator-like ATLAS robot from Boston Dynamics, alongside Korean robot HUBO, took many of the plaudits, and CHIMP also put in an impressive display by being able to right itself after falling.

Yet the DARPA Robotics Challenge showed us just how far the robots are from truly being as useful as we’d like, or maybe even as we would imagine. Many robots took hours to complete the tasks, which were highly idealized to suit them. Climbing stairs proved a particular challenge. Those who watched were more likely to see a robot that had fallen over, struggling to get up, rather than heroic superbots striding in to save the day. The “striding” proved a particular problem, with the fastest robot HUBO managing this by resorting to wheels in its knees when the legs weren’t necessary.

Fukushima may have brought a sea-change over futuristic Japan, but before robots will really begin to enter our everyday lives, they will need to prove their worth. In the interim, aerial drone robots designed to examine infrastructure damage after disasters may well see earlier deployment and more success.

It’s a considerable challenge.

Building a humanoid robot is expensive; if these multi-million-dollar machines can’t help in a crisis, people may begin to question the worth of investing in them in the first place (unless your aim is just to make viral videos). This could lead to a further crisis of confidence among the Japanese, who are starting to rely on humanoid robotics as a solution to the crisis of the aging population. The Japanese government, as part of its robots strategy, has already invested $44 million in their development.

But if they continue to fail when put to the test, that will raise serious concerns. In Tokyo’s Akihabara district, you can see all kinds of flash robotic toys for sale in the neon-lit superstores, and dancing, acting robots like Robothespian can entertain crowds all over the world. But if we want these machines to be anything more than toys—partners, helpers, even saviors—more work needs to be done.

At the same time, those who participated in the DARPA Robotics Challenge in 2015 won’t be too concerned if people were underwhelmed by the performance of their disaster relief robots. Back in 2004, nearly every participant in the DARPA Grand Challenge crashed, caught fire, or failed on the starting line. To an outside observer, the whole thing would have seemed like an unmitigated disaster, and a pointless investment. What was the task in 2004? Developing a self-driving car. A lot can change in a decade.

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#432456 This Planned Solar Farm in Saudi Arabia ...

Right now it only exists on paper, in the form of a memorandum of understanding. But if constructed, the newly-announced solar photovoltaic project in Saudi Arabia would break an astonishing array of records. It’s larger than any solar project currently planned by a factor of 100. When completed, nominally in 2030, it would have a capacity of an astonishing 200 gigawatts (GW). The project is backed by Softbank Group and Saudi Arabia’s new crown prince, Mohammed Bin Salman, and was announced in New York on March 27.

The Tengger Desert Solar Park in China, affectionately known as the “Great Wall of Solar,” is the world’s largest operating solar farm, with a capacity of 1.5 GW. Larger farms are under construction, including the Westlands Solar Park, which plans to finish with 2.7 GW of capacity. But even those that are only in the planning phases are dwarfed by the Saudi project; two early-stage solar parks will have capacity of 7.2 GW, and the plan involves them generating electricity as early as next year.

It makes more sense to compare to slightly larger projects, like nations, or even planets. Saudi Arabia’s current electricity generation capacity is 77 GW. This project would almost triple it. The current total solar photovoltaic generation capacity installed worldwide is 303 GW. In other words, this single solar farm would account for a similar installed capacity as the entire world’s capacity in 2015, and over a thousand times more than we had in 2000.

That’s exponential growth for you, folks.

Of course, practically doubling the world’s solar capacity doesn’t come cheap; the nominal estimate for the budget is around $200 billion (compared to $20 billion for around half a gigawatt of fusion, though, it may not seem so bad.) But the project would help solve a number of pressing problems for Saudi Arabia.

For a start, solar power works well in the desert. The irradiance is high, you have plenty of empty space, and peak demand is driven by air conditioning in the cities and so corresponds with peak supply. Even if oil companies might seem blasé about the global supply of oil running out, individual countries are aware that their own reserves won’t last forever, and they don’t want to miss the energy transition. The country’s Vision 2030 project aims to diversify its heavily oil-dependent economy by that year. If they can construct solar farms on this scale, alongside the $80 billion the government plans to spend on a fleet of nuclear reactors, it seems logical to export that power to other countries in the region, especially given the amount of energy storage that would be required otherwise.

We’ve already discussed a large-scale project to build solar panels in the desert then export the electricity: the DESERTEC initiative in the Sahara. Although DESERTEC planned a range of different demonstration plants on scales of around 500 MW, its ultimate ambition was to “provide 20 percent of Europe’s electricity by 2050.” It seems that this project is similar in scale to what they were planning. Weaning ourselves off fossil fuels is going to be incredibly difficult. Only large-scale nuclear, wind, or solar can really supply the world’s energy needs if consumption is anything like what it is today; in all likelihood, we’ll need a combination of all three.

To make a sizeable contribution to that effort, the renewable projects have to be truly epic in scale. The planned 2 GW solar park at Bulli Creek in Australia would cover 5 square kilometers, so it’s not unreasonable to suggest that, across many farms, this project could cover around 500 square kilometers—around the size of Chicago.

It will come as no surprise that Softbank is involved in this project. The founder, Masayoshi Son, is well-known for large-scale “visionary” investments. This is suggested by the name of his $100 billion VC fund, the Softbank Vision Fund, and the focus of its investments. It has invested millions of dollars in tech companies like Uber, IoT, NVIDIA and ARM, and startups across fields like VR, agritech, and AI.

Of course, Softbank is also the company that bought infamous robot-makers Boston Dynamics from Google when their not-at-all-sinister “Project Replicant” was sidelined. Softbank is famous in Japan in part due to their mascot, Pepper, which is probably the most widespread humanoid robot on the planet. Suffice it to say that Softbank is keen to be a part of any technological development, and they’re not afraid of projects that are truly vast in scope.

Since the Fukushima disaster in 2011 led Japan to turn away from nuclear power, Son has also been focused on green electricity, floating the idea of an Asia Super Grid. Similar to DESERTEC, it aims to get around the main issues with renewable energy (the land use and the intermittency of supply) with a vast super-grid that would connect Mongolia, India, Japan, China, Russia, and South Korea with high-voltage DC power cables. “Since this is such a grandiose project, many people told me it is crazy,” Son said. “They said it is impossible both economically and politically.” The first stage of the project, a demonstration wind farm of 50 megawatts in Mongolia, began operating in October of last year.

Given that Saudi Arabia put up $45 billion of the Vision Fund, it’s also not surprising to see the location of the project; Softbank reportedly had plans to invest $25 billion of the Vision Fund in Saudi Arabia, and $1 billion will be spent on the first solar farms there. Prince Mohammed Bin Salman, 32, who recently consolidated power, is looking to be seen on the global stage as a modernizer. He was effusive about the project. “It’s a huge step in human history,” he said. “It’s bold, risky, and we hope we succeed doing that.”

It is the risk that will keep renewable energy enthusiasts concerned.

Every visionary plan contains the potential for immense disappointment. As yet, the Asian Super Grid and the Saudi power plan are more or less at the conceptual stage. The fact that a memorandum of understanding exists between the Saudi government and Softbank is no guarantee that it will ever be built. Some analysts in the industry are a little skeptical.

“It’s an unprecedented construction effort; it’s an unprecedented financing effort,” said Benjamin Attia, a global solar analyst for Green Tech Media Research. “But there are so many questions, so few details, and a lot of headwinds, like grid instability, the availability of commercial debt, construction, and logistics challenges.”

We have already seen with the DESERTEC initiative that these vast-scale renewable energy projects can fail, despite immense enthusiasm. They are not easy to accomplish. But in a world without fossil fuels, they will be required. This project could be a flagship example for how to run a country on renewable energy—or another example of grand designs and good intentions. We’ll have to wait to find out which.

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#432165 Silicon Valley Is Winning the Race to ...

Henry Ford didn’t invent the motor car. The late 1800s saw a flurry of innovation by hundreds of companies battling to deliver on the promise of fast, efficient and reasonably-priced mechanical transportation. Ford later came to dominate the industry thanks to the development of the moving assembly line.

Today, the sector is poised for another breakthrough with the advent of cars that drive themselves. But unlike the original wave of automobile innovation, the race for supremacy in autonomous vehicles is concentrated among a few corporate giants. So who is set to dominate this time?

I’ve analyzed six companies we think are leading the race to build the first truly driverless car. Three of these—General Motors, Ford, and Volkswagen—come from the existing car industry and need to integrate self-driving technology into their existing fleet of mass-produced vehicles. The other three—Tesla, Uber, and Waymo (owned by the same company as Google)—are newcomers from the digital technology world of Silicon Valley and have to build a mass manufacturing capability.

While it’s impossible to know all the developments at any given time, we have tracked investments, strategic partnerships, and official press releases to learn more about what’s happening behind the scenes. The car industry typically rates self-driving technology on a scale from Level 0 (no automation) to Level 5 (full automation). We’ve assessed where each company is now and estimated how far they are from reaching the top level. Here’s how we think each player is performing.

Volkswagen
Volkswagen has invested in taxi-hailing app Gett and partnered with chip-maker Nvidia to develop an artificial intelligence co-pilot for its cars. In 2018, the VW Group is set to release the Audi A8, the first production vehicle that reaches Level 3 on the scale, “conditional driving automation.” This means the car’s computer will handle all driving functions, but a human has to be ready to take over if necessary.

Ford
Ford already sells cars with a Level 2 autopilot, “partial driving automation.” This means one or more aspects of driving are controlled by a computer based on information about the environment, for example combined cruise control and lane centering. Alongside other investments, the company has put $1 billion into Argo AI, an artificial intelligence company for self-driving vehicles. Following a trial to test pizza delivery using autonomous vehicles, Ford is now testing Level 4 cars on public roads. These feature “high automation,” where the car can drive entirely on its own but not in certain conditions such as when the road surface is poor or the weather is bad.

General Motors
GM also sells vehicles with Level 2 automation but, after buying Silicon Valley startup Cruise Automation in 2016, now plans to launch the first mass-production-ready Level 5 autonomy vehicle that drives completely on its own by 2019. The Cruise AV will have no steering wheel or pedals to allow a human to take over and be part of a large fleet of driverless taxis the company plans to operate in big cities. But crucially the company hasn’t yet secured permission to test the car on public roads.

Waymo (Google)

Waymo Level 5 testing. Image Credit: Waymo

Founded as a special project in 2009, Waymo separated from Google (though they’re both owned by the same parent firm, Alphabet) in 2016. Though it has never made, sold, or operated a car on a commercial basis, Waymo has created test vehicles that have clocked more than 4 million miles without human drivers as of November 2017. Waymo tested its Level 5 car, “Firefly,” between 2015 and 2017 but then decided to focus on hardware that could be installed in other manufacturers’ vehicles, starting with the Chrysler Pacifica.

Uber
The taxi-hailing app maker Uber has been testing autonomous cars on the streets of Pittsburgh since 2016, always with an employee behind the wheel ready to take over in case of a malfunction. After buying the self-driving truck company Otto in 2016 for a reported $680 million, Uber is now expanding its AI capabilities and plans to test NVIDIA’s latest chips in Otto’s vehicles. It has also partnered with Volvo to create a self-driving fleet of cars and with Toyota to co-create a ride-sharing autonomous vehicle.

Tesla
The first major car manufacturer to come from Silicon Valley, Tesla was also the first to introduce Level 2 autopilot back in 2015. The following year, it announced that all new Teslas would have the hardware for full autonomy, meaning once the software is finished it can be deployed on existing cars with an instant upgrade. Some experts have challenged this approach, arguing that the company has merely added surround cameras to its production cars that aren’t as capable as the laser-based sensing systems that most other carmakers are using.

But the company has collected data from hundreds of thousands of cars, driving millions of miles across all terrains. So, we shouldn’t dismiss the firm’s founder, Elon Musk, when he claims a Level 4 Tesla will drive from LA to New York without any human interference within the first half of 2018.

Winners

Who’s leading the race? Image Credit: IMD

At the moment, the disruptors like Tesla, Waymo, and Uber seem to have the upper hand. While the traditional automakers are focusing on bringing Level 3 and 4 partial automation to market, the new companies are leapfrogging them by moving more directly towards Level 5 full automation. Waymo may have the least experience of dealing with consumers in this sector, but it has already clocked up a huge amount of time testing some of the most advanced technology on public roads.

The incumbent carmakers are also focused on the difficult process of integrating new technology and business models into their existing manufacturing operations by buying up small companies. The challengers, on the other hand, are easily partnering with other big players including manufacturers to get the scale and expertise they need more quickly.

Tesla is building its own manufacturing capability but also collecting vast amounts of critical data that will enable it to more easily upgrade its cars when ready for full automation. In particular, Waymo’s experience, technology capability, and ability to secure solid partnerships puts it at the head of the pack.

This article was originally published on The Conversation. Read the original article.

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