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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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#434270 AI Will Create Millions More Jobs Than ...

In the past few years, artificial intelligence has advanced so quickly that it now seems hardly a month goes by without a newsworthy AI breakthrough. In areas as wide-ranging as speech translation, medical diagnosis, and gameplay, we have seen computers outperform humans in startling ways.

This has sparked a discussion about how AI will impact employment. Some fear that as AI improves, it will supplant workers, creating an ever-growing pool of unemployable humans who cannot compete economically with machines.

This concern, while understandable, is unfounded. In fact, AI will be the greatest job engine the world has ever seen.

New Technology Isn’t a New Phenomenon
On the one hand, those who predict massive job loss from AI can be excused. It is easier to see existing jobs disrupted by new technology than to envision what new jobs the technology will enable.

But on the other hand, radical technological advances aren’t a new phenomenon. Technology has progressed nonstop for 250 years, and in the US unemployment has stayed between 5 to 10 percent for almost all that time, even when radical new technologies like steam power and electricity came on the scene.

But you don’t have to look back to steam, or even electricity. Just look at the internet. Go back 25 years, well within the memory of today’s pessimistic prognosticators, to 1993. The web browser Mosaic had just been released, and the phrase “surfing the web,” that most mixed of metaphors, was just a few months old.

If someone had asked you what would be the result of connecting a couple billion computers into a giant network with common protocols, you might have predicted that email would cause us to mail fewer letters, and the web might cause us to read fewer newspapers and perhaps even do our shopping online. If you were particularly farsighted, you might have speculated that travel agents and stockbrokers would be adversely affected by this technology. And based on those surmises, you might have thought the internet would destroy jobs.

But now we know what really happened. The obvious changes did occur. But a slew of unexpected changes happened as well. We got thousands of new companies worth trillions of dollars. We bettered the lot of virtually everyone on the planet touched by the technology. Dozens of new careers emerged, from web designer to data scientist to online marketer. The cost of starting a business with worldwide reach plummeted, and the cost of communicating with customers and leads went to nearly zero. Vast storehouses of information were made freely available and used by entrepreneurs around the globe to build new kinds of businesses.

But yes, we mail fewer letters and buy fewer newspapers.

The Rise of Artificial Intelligence
Then along came a new, even bigger technology: artificial intelligence. You hear the same refrain: “It will destroy jobs.”

Consider the ATM. If you had to point to a technology that looked as though it would replace people, the ATM might look like a good bet; it is, after all, an automated teller machine. And yet, there are more tellers now than when ATMs were widely released. How can this be? Simple: ATMs lowered the cost of opening bank branches, and banks responded by opening more, which required hiring more tellers.

In this manner, AI will create millions of jobs that are far beyond our ability to imagine. For instance, AI is becoming adept at language translation—and according to the US Bureau of Labor Statistics, demand for human translators is skyrocketing. Why? If the cost of basic translation drops to nearly zero, the cost of doing business with those who speak other languages falls. Thus, it emboldens companies to do more business overseas, creating more work for human translators. AI may do the simple translations, but humans are needed for the nuanced kind.

In fact, the BLS forecasts faster-than-average job growth in many occupations that AI is expected to impact: accountants, forensic scientists, geological technicians, technical writers, MRI operators, dietitians, financial specialists, web developers, loan officers, medical secretaries, and customer service representatives, to name a very few. These fields will not experience job growth in spite of AI, but through it.

But just as with the internet, the real gains in jobs will come from places where our imaginations cannot yet take us.

Parsing Pessimism
You may recall waking up one morning to the news that “47 percent of jobs will be lost to technology.”

That report by Carl Frey and Michael Osborne is a fine piece of work, but readers and the media distorted their 47 percent number. What the authors actually said is that some functions within 47 percent of jobs will be automated, not that 47 percent of jobs will disappear.

Frey and Osborne go on to rank occupations by “probability of computerization” and give the following jobs a 65 percent or higher probability: social science research assistants, atmospheric and space scientists, and pharmacy aides. So what does this mean? Social science professors will no longer have research assistants? Of course they will. They will just do different things because much of what they do today will be automated.

The intergovernmental Organization for Economic Co-operation and Development released a report of their own in 2016. This report, titled “The Risk of Automation for Jobs in OECD Countries,” applies a different “whole occupations” methodology and puts the share of jobs potentially lost to computerization at nine percent. That is normal churn for the economy.

But what of the skills gap? Will AI eliminate low-skilled workers and create high-skilled job opportunities? The relevant question is whether most people can do a job that’s just a little more complicated than the one they currently have. This is exactly what happened with the industrial revolution; farmers became factory workers, factory workers became factory managers, and so on.

Embracing AI in the Workplace
A January 2018 Accenture report titled “Reworking the Revolution” estimates that new applications of AI combined with human collaboration could boost employment worldwide as much as 10 percent by 2020.

Electricity changed the world, as did mechanical power, as did the assembly line. No one can reasonably claim that we would be better off without those technologies. Each of them bettered our lives, created jobs, and raised wages. AI will be bigger than electricity, bigger than mechanization, bigger than anything that has come before it.

This is how free economies work, and why we have never run out of jobs due to automation. There are not a fixed number of jobs that automation steals one by one, resulting in progressively more unemployment. There are as many jobs in the world as there are buyers and sellers of labor.

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#434256 Singularity Hub’s Top Articles of the ...

2018 was a big year for science and technology. The first gene-edited babies were born, as were the first cloned monkeys. SpaceX successfully launched the Falcon Heavy, and NASA’s InSight lander placed a seismometer on Mars. Bitcoin’s value plummeted, as did the cost of renewable energy. The world’s biggest neuromorphic supercomputer was switched on, and quantum communication made significant progress.

As 2018 draws to a close and we start anticipating the developments that will happen in 2019, here’s a look back at our ten most-read articles of the year.

This 3D Printed House Goes Up in a Day for Under $10,000
Vanessa Bates Ramirez | 3/18/18
“ICON and New Story’s vision is one of 3D printed houses acting as a safe, affordable housing alternative for people in need. New Story has already built over 800 homes in Haiti, El Salvador, Bolivia, and Mexico, partnering with the communities they serve to hire local labor and purchase local materials rather than shipping everything in from abroad.”

Machines Teaching Each Other Could Be the Biggest Exponential Trend in AI
Aaron Frank | 1/21/18
“Data is the fuel of machine learning, but even for machines, some data is hard to get—it may be risky, slow, rare, or expensive. In those cases, machines can share experiences or create synthetic experiences for each other to augment or replace data. It turns out that this is not a minor effect, it actually is self-amplifying, and therefore exponential.”

Low-Cost Soft Robot Muscles Can Lift 200 Times Their Weight and Self-Heal
Edd Gent | 1/11/18
“Now researchers at the University of Colorado Boulder have built a series of low-cost artificial muscles—as little as 10 cents per device—using soft plastic pouches filled with electrically insulating liquids that contract with the force and speed of mammalian skeletal muscles when a voltage is applied to them.”

These Are the Most Exciting Industries and Jobs of the Future
Raya Bidshahri | 1/29/18
“Technological trends are giving rise to what many thought leaders refer to as the “imagination economy.” This is defined as “an economy where intuitive and creative thinking create economic value, after logical and rational thinking have been outsourced to other economies.” Unsurprisingly, humans continue to outdo machines when it comes to innovating and pushing intellectual, imaginative, and creative boundaries, making jobs involving these skills the hardest to automate.”

Inside a $1 Billion Real Estate Company Operating Entirely in VR
Aaron Frank | 4/8/18
“Incredibly, this growth is largely the result of eXp Realty’s use of an online virtual world similar to Second Life. That means every employee, contractor, and the thousands of agents who work at the company show up to work—team meetings, training seminars, onboarding sessions—all inside a virtual reality campus.To be clear, this is a traditional real estate brokerage helping people buy and sell physical homes—but they use a virtual world as their corporate offices.”

How Fast Is AI Progressing? Stanford’s New Report Card for Artificial Intelligence
Thomas Hornigold | 1/18/18
“Progress in AI over the next few years is far more likely to resemble a gradual rising tide—as more and more tasks can be turned into algorithms and accomplished by software—rather than the tsunami of a sudden intelligence explosion or general intelligence breakthrough. Perhaps measuring the ability of an AI system to learn and adapt to the work routines of humans in office-based tasks could be possible.”

When Will We Finally Achieve True Artificial Intelligence?
Thomas Hornigold | 1/1/18
“The issue with trying to predict the exact date of human-level AI is that we don’t know how far is left to go. This is unlike Moore’s Law. Moore’s Law, the doubling of processing power roughly every couple of years, makes a very concrete prediction about a very specific phenomenon. We understand roughly how to get there—improved engineering of silicon wafers—and we know we’re not at the fundamental limits of our current approach. You cannot say the same about artificial intelligence.”

IBM’s New Computer Is the Size of a Grain of Salt and Costs Less Than 10 Cents
Edd Gent | 3/26/18
“Costing less than 10 cents to manufacture, the company envisions the device being embedded into products as they move around the supply chain. The computer’s sensing, processing, and communicating capabilities mean it could effectively turn every item in the supply chain into an Internet of Things device, producing highly granular supply chain data that could streamline business operations.”

Why the Rise of Self-Driving Vehicles Will Actually Increase Car Ownership
Melba Kurman and Hod Lipson / 2/14/18
“When people predict the demise of car ownership, they are overlooking the reality that the new autonomous automotive industry is not going to be just a re-hash of today’s car industry with driverless vehicles. Instead, the automotive industry of the future will be selling what could be considered an entirely new product: a wide variety of intelligent, self-guiding transportation robots. When cars become a widely used type of transportation robot, they will be cheap, ubiquitous, and versatile.”

A Model for the Future of Education
Peter Diamandis | 9/12/18
“I imagine a relatively near-term future in which robotics and artificial intelligence will allow any of us, from ages 8 to 108, to easily and quickly find answers, create products, or accomplish tasks, all simply by expressing our desires. From ‘mind to manufactured in moments.’ In short, we’ll be able to do and create almost whatever we want. In this future, what attributes will be most critical for our children to learn to become successful in their adult lives? What’s most important for educating our children today?”

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#434235 The Milestones of Human Progress We ...

When you look back at 2018, do you see a good or a bad year? Chances are, your perception of the year involves fixating on all the global and personal challenges it brought. In fact, every year, we tend to look back at the previous year as “one of the most difficult” and hope that the following year is more exciting and fruitful.

But in the grander context of human history, 2018 was an extraordinarily positive year. In fact, every year has been getting progressively better.

Before we dive into some of the highlights of human progress from 2018, let’s make one thing clear. There is no doubt that there are many overwhelming global challenges facing our species. From climate change to growing wealth inequality, we are far from living in a utopia.

Yet it’s important to recognize that both our news outlets and audiences have been disproportionately fixated on negative news. This emphasis on bad news is detrimental to our sense of empowerment as a species.

So let’s take a break from all the disproportionate negativity and have a look back on how humanity pushed boundaries in 2018.

On Track to Becoming an Interplanetary Species
We often forget how far we’ve come since the very first humans left the African savanna, populated the entire planet, and developed powerful technological capabilities. Our desire to explore the unknown has shaped the course of human evolution and will continue to do so.

This year, we continued to push the boundaries of space exploration. As depicted in the enchanting short film Wanderers, humanity’s destiny is the stars. We are born to be wanderers of the cosmos and the everlasting unknown.

SpaceX had 21 successful launches in 2018 and closed the year with a successful GPS launch. The latest test flight by Virgin Galactic was also an incredible milestone, as SpaceShipTwo was welcomed into space. Richard Branson and his team expect that space tourism will be a reality within the next 18 months.

Our understanding of the cosmos is also moving forward with continuous breakthroughs in astrophysics and astronomy. One notable example is the MARS InSight Mission, which uses cutting-edge instruments to study Mars’ interior structure and has even given us the first recordings of sound on Mars.

Understanding and Tackling Disease
Thanks to advancements in science and medicine, we are currently living longer, healthier, and wealthier lives than at any other point in human history. In fact, for most of human history, life expectancy at birth was around 30. Today it is more than 70 worldwide, and in the developed parts of the world, more than 80.

Brilliant researchers around the world are pushing for even better health outcomes. This year, we saw promising treatments emerge against Alzheimers disease, rheumatoid arthritis, multiple scleroris, and even the flu.

The deadliest disease of them all, cancer, is also being tackled. According to the American Association of Cancer Research, 22 revolutionary treatments for cancer were approved in the last year, and the death rate in adults is also in decline. Advancements in immunotherapy, genetic engineering, stem cells, and nanotechnology are all powerful resources to tackle killer diseases.

Breakthrough Mental Health Therapy
While cleaner energy, access to education, and higher employment rates can improve quality of life, they do not guarantee happiness and inner peace. According to the World Economic Forum, mental health disorders affect one in four people globally, and in many places they are significantly under-reported. More people are beginning to realize that our mental health is just as important as our physical health, and that we ought to take care of our minds just as much as our bodies.

We are seeing the rise of applications that put mental well-being at their center. Breakthrough advancements in genetics are allowing us to better understand the genetic makeup of disorders like clinical depression or Schizophrenia, and paving the way for personalized medical treatment. We are also seeing the rise of increasingly effective therapeutic treatments for anxiety.

This year saw many milestones for a whole new revolutionary area in mental health: psychedelic therapy. Earlier this summer, the FDA granted breakthrough therapy designation to MDMA for the treatment of PTSD, after several phases of successful trails. Similar research has discovered that Psilocybin (also known as magic mushrooms) combined with therapy is far more effective than traditional forms of treatment for depression and anxiety.

Moral and Social Progress
Innovation is often associated with economic and technological progress. However, we also need leaps of progress in our morality, values, and policies. Throughout the 21st century, we’ve made massive strides in rights for women and children, civil rights, LGBT rights, animal rights, and beyond. However, with rising nationalism and xenophobia in many parts of the developed world, there is significant work to be done on this front.

All hope is not lost, as we saw many noteworthy milestones this year. In January 2018, Iceland introduced the equal wage law, bringing an end to the gender wage gap. On September 6th, the Indian Supreme Court decriminalized homosexuality, marking a historical moment. Earlier in December, the European Commission released a draft of ethics guidelines for trustworthy artificial intelligence. Such are just a few examples of positive progress in social justice, ethics, and policy.

We are also seeing a global rise in social impact entrepreneurship. Emerging startups are no longer valued simply based on their profits and revenue, but also on the level of positive impact they are having on the world at large. The world’s leading innovators are not asking themselves “How can I become rich?” but rather “How can I solve this global challenge?”

Intelligently Optimistic for 2019
It’s becoming more and more clear that we are living in the most exciting time in human history. Even more, we mustn’t be afraid to be optimistic about 2019.

An optimistic mindset can be grounded in rationality and evidence. Intelligent optimism is all about being excited about the future in an informed and rational way. The mindset is critical if we are to get everyone excited about the future by highlighting the rapid progress we have made and recognizing the tremendous potential humans have to find solutions to our problems.

In his latest TED talk, Steven Pinker points out, “Progress does not mean that everything becomes better for everyone everywhere all the time. That would be a miracle, and progress is not a miracle but problem-solving. Problems are inevitable and solutions create new problems which have to be solved in their turn.”

Let us not forget that in cosmic time scales, our entire species’ lifetime, including all of human history, is the equivalent of the blink of an eye. The probability of us existing both as an intelligent species and as individuals is so astoundingly low that it’s practically non-existent. We are the products of 14 billion years of cosmic evolution and extraordinarily good fortune. Let’s recognize and leverage this wondrous opportunity, and pave an exciting way forward.

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#434151 Life-or-Death Algorithms: The Black Box ...

When it comes to applications for machine learning, few can be more widely hyped than medicine. This is hardly surprising: it’s a huge industry that generates a phenomenal amount of data and revenue, where technological advances can improve or save the lives of millions of people. Hardly a week passes without a study that suggests algorithms will soon be better than experts at detecting pneumonia, or Alzheimer’s—diseases in complex organs ranging from the eye to the heart.

The problems of overcrowded hospitals and overworked medical staff plague public healthcare systems like Britain’s NHS and lead to rising costs for private healthcare systems. Here, again, algorithms offer a tantalizing solution. How many of those doctor’s visits really need to happen? How many could be replaced by an interaction with an intelligent chatbot—especially if it can be combined with portable diagnostic tests, utilizing the latest in biotechnology? That way, unnecessary visits could be reduced, and patients could be diagnosed and referred to specialists more quickly without waiting for an initial consultation.

As ever with artificial intelligence algorithms, the aim is not to replace doctors, but to give them tools to reduce the mundane or repetitive parts of the job. With an AI that can examine thousands of scans in a minute, the “dull drudgery” is left to machines, and the doctors are freed to concentrate on the parts of the job that require more complex, subtle, experience-based judgement of the best treatments and the needs of the patient.

High Stakes
But, as ever with AI algorithms, there are risks involved with relying on them—even for tasks that are considered mundane. The problems of black-box algorithms that make inexplicable decisions are bad enough when you’re trying to understand why that automated hiring chatbot was unimpressed by your job interview performance. In a healthcare context, where the decisions made could mean life or death, the consequences of algorithmic failure could be grave.

A new paper in Science Translational Medicine, by Nicholson Price, explores some of the promises and pitfalls of using these algorithms in the data-rich medical environment.

Neural networks excel at churning through vast quantities of training data and making connections, absorbing the underlying patterns or logic for the system in hidden layers of linear algebra; whether it’s detecting skin cancer from photographs or learning to write in pseudo-Shakespearean script. They are terrible, however, at explaining the underlying logic behind the relationships that they’ve found: there is often little more than a string of numbers, the statistical “weights” between the layers. They struggle to distinguish between correlation and causation.

This raises interesting dilemmas for healthcare providers. The dream of big data in medicine is to feed a neural network on “huge troves of health data, finding complex, implicit relationships and making individualized assessments for patients.” What if, inevitably, such an algorithm proves to be unreasonably effective at diagnosing a medical condition or prescribing a treatment, but you have no scientific understanding of how this link actually works?

Too Many Threads to Unravel?
The statistical models that underlie such neural networks often assume that variables are independent of each other, but in a complex, interacting system like the human body, this is not always the case.

In some ways, this is a familiar concept in medical science—there are many phenomena and links which have been observed for decades but are still poorly understood on a biological level. Paracetamol is one of the most commonly-prescribed painkillers, but there’s still robust debate about how it actually works. Medical practitioners may be keen to deploy whatever tool is most effective, regardless of whether it’s based on a deeper scientific understanding. Fans of the Copenhagen interpretation of quantum mechanics might spin this as “Shut up and medicate!”

But as in that field, there’s a debate to be had about whether this approach risks losing sight of a deeper understanding that will ultimately prove more fruitful—for example, for drug discovery.

Away from the philosophical weeds, there are more practical problems: if you don’t understand how a black-box medical algorithm is operating, how should you approach the issues of clinical trials and regulation?

Price points out that, in the US, the “21st-Century Cures Act” allows the FDA to regulate any algorithm that analyzes images, or doesn’t allow a provider to review the basis for its conclusions: this could completely exclude “black-box” algorithms of the kind described above from use.

Transparency about how the algorithm functions—the data it looks at, and the thresholds for drawing conclusions or providing medical advice—may be required, but could also conflict with the profit motive and the desire for secrecy in healthcare startups.

One solution might be to screen algorithms that can’t explain themselves, or don’t rely on well-understood medical science, from use before they enter the healthcare market. But this could prevent people from reaping the benefits that they can provide.

Evaluating Algorithms
New healthcare algorithms will be unable to do what physicists did with quantum mechanics, and point to a track record of success, because they will not have been deployed in the field. And, as Price notes, many algorithms will improve as they’re deployed in the field for a greater amount of time, and can harvest and learn from the performance data that’s actually used. So how can we choose between the most promising approaches?

Creating a standardized clinical trial and validation system that’s equally valid across algorithms that function in different ways, or use different input or training data, will be a difficult task. Clinical trials that rely on small sample sizes, such as for algorithms that attempt to personalize treatment to individuals, will also prove difficult. With a small sample size and little scientific understanding, it’s hard to tell whether the algorithm succeeded or failed because it’s bad at its job or by chance.

Add learning into the mix and the picture gets more complex. “Perhaps more importantly, to the extent that an ideal black-box algorithm is plastic and frequently updated, the clinical trial validation model breaks down further, because the model depends on a static product subject to stable validation.” As Price describes, the current system for testing and validation of medical products needs some adaptation to deal with this new software before it can successfully test and validate the new algorithms.

Striking a Balance
The story in healthcare reflects the AI story in so many other fields, and the complexities involved perhaps illustrate why even an illustrious company like IBM appears to be struggling to turn its famed Watson AI into a viable product in the healthcare space.

A balance must be struck, both in our rush to exploit big data and the eerie power of neural networks, and to automate thinking. We must be aware of the biases and flaws of this approach to problem-solving: to realize that it is not a foolproof panacea.

But we also need to embrace these technologies where they can be a useful complement to the skills, insights, and deeper understanding that humans can provide. Much like a neural network, our industries need to train themselves to enhance this cooperation in the future.

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