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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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#434508 The Top Biotech and Medicine Advances to ...

2018 was bonkers for science.

From a woman who gave birth using a transplanted uterus, to the infamous CRISPR baby scandal, to forensics adopting consumer-based genealogy test kits to track down criminals, last year was a factory churning out scientific “whoa” stories with consequences for years to come.

With CRISPR still in the headlines, Britain ready to bid Europe au revoir, and multiple scientific endeavors taking off, 2019 is shaping up to be just as tumultuous.

Here are the science and health stories that may blow up in the new year. But first, a note of caveat: predicting the future is tough. Forecasting is the lovechild between statistics and (a good deal of) intuition, and entire disciplines have been dedicated to the endeavor. But January is the perfect time to gaze into the crystal ball for wisps of insight into the year to come. Last year we predicted the widespread approval of gene therapy products—on the most part, we nailed it. This year we’re hedging our bets with multiple predictions.

Gene Drives Used in the Wild
The concept of gene drives scares many, for good reason. Gene drives are a step up in severity (and consequences) from CRISPR and other gene-editing tools. Even with germline editing, in which the sperm, egg, or embryos are altered, gene editing affects just one genetic line—one family—at least at the beginning, before they reproduce with the general population.

Gene drives, on the other hand, have the power to wipe out entire species.

In a nutshell, they’re little bits of DNA code that help a gene transfer from parent to child with almost 100 percent perfect probability. The “half of your DNA comes from dad, the other comes from mom” dogma? Gene drives smash that to bits.

In other words, the only time one would consider using a gene drive is to change the genetic makeup of an entire population. It sounds like the plot of a supervillain movie, but scientists have been toying around with the idea of deploying the technology—first in mosquitoes, then (potentially) in rodents.

By releasing just a handful of mutant mosquitoes that carry gene drives for infertility, for example, scientists could potentially wipe out entire populations that carry infectious scourges like malaria, dengue, or Zika. The technology is so potent—and dangerous—the US Defense Advances Research Projects Agency is shelling out $65 million to suss out how to deploy, control, counter, or even reverse the effects of tampering with ecology.

Last year, the U.N. gave a cautious go-ahead for the technology to be deployed in the wild in limited terms. Now, the first release of a genetically modified mosquito is set for testing in Burkina Faso in Africa—the first-ever field experiment involving gene drives.

The experiment will only release mosquitoes in the Anopheles genus, which are the main culprits transferring disease. As a first step, over 10,000 male mosquitoes are set for release into the wild. These dudes are genetically sterile but do not cause infertility, and will help scientists examine how they survive and disperse as a preparation for deploying gene-drive-carrying mosquitoes.

Hot on the project’s heels, the nonprofit consortium Target Malaria, backed by the Bill and Melinda Gates foundation, is engineering a gene drive called Mosq that will spread infertility across the population or kill out all female insects. Their attempt to hack the rules of inheritance—and save millions in the process—is slated for 2024.

A Universal Flu Vaccine
People often brush off flu as a mere annoyance, but the infection kills hundreds of thousands each year based on the CDC’s statistical estimates.

The flu virus is actually as difficult of a nemesis as HIV—it mutates at an extremely rapid rate, making effective vaccines almost impossible to engineer on time. Scientists currently use data to forecast the strains that will likely explode into an epidemic and urge the public to vaccinate against those predictions. That’s partly why, on average, flu vaccines only have a success rate of roughly 50 percent—not much better than a coin toss.

Tired of relying on educated guesses, scientists have been chipping away at a universal flu vaccine that targets all strains—perhaps even those we haven’t yet identified. Often referred to as the “holy grail” in epidemiology, these vaccines try to alert our immune systems to parts of a flu virus that are least variable from strain to strain.

Last November, a first universal flu vaccine developed by BiondVax entered Phase 3 clinical trials, which means it’s already been proven safe and effective in a small numbers and is now being tested in a broader population. The vaccine doesn’t rely on dead viruses, which is a common technique. Rather, it uses a small chain of amino acids—the chemical components that make up proteins—to stimulate the immune system into high alert.

With the government pouring $160 million into the research and several other universal candidates entering clinical trials, universal flu vaccines may finally experience a breakthrough this year.

In-Body Gene Editing Shows Further Promise
CRISPR and other gene editing tools headed the news last year, including both downers suggesting we already have immunity to the technology and hopeful news of it getting ready for treating inherited muscle-wasting diseases.

But what wasn’t widely broadcasted was the in-body gene editing experiments that have been rolling out with gusto. Last September, Sangamo Therapeutics in Richmond, California revealed that they had injected gene-editing enzymes into a patient in an effort to correct a genetic deficit that prevents him from breaking down complex sugars.

The effort is markedly different than the better-known CAR-T therapy, which extracts cells from the body for genetic engineering before returning them to the hosts. Rather, Sangamo’s treatment directly injects viruses carrying the edited genes into the body. So far, the procedure looks to be safe, though at the time of reporting it was too early to determine effectiveness.

This year the company hopes to finally answer whether it really worked.

If successful, it means that devastating genetic disorders could potentially be treated with just a few injections. With a gamut of new and more precise CRISPR and other gene-editing tools in the works, the list of treatable inherited diseases is likely to grow. And with the CRISPR baby scandal potentially dampening efforts at germline editing via regulations, in-body gene editing will likely receive more attention if Sangamo’s results return positive.

Neuralink and Other Brain-Machine Interfaces
Neuralink is the stuff of sci fi: tiny implanted particles into the brain could link up your biological wetware with silicon hardware and the internet.

But that’s exactly what Elon Musk’s company, founded in 2016, seeks to develop: brain-machine interfaces that could tinker with your neural circuits in an effort to treat diseases or even enhance your abilities.

Last November, Musk broke his silence on the secretive company, suggesting that he may announce something “interesting” in a few months, that’s “better than anyone thinks is possible.”

Musk’s aspiration for achieving symbiosis with artificial intelligence isn’t the driving force for all brain-machine interfaces (BMIs). In the clinics, the main push is to rehabilitate patients—those who suffer from paralysis, memory loss, or other nerve damage.

2019 may be the year that BMIs and neuromodulators cut the cord in the clinics. These devices may finally work autonomously within a malfunctioning brain, applying electrical stimulation only when necessary to reduce side effects without requiring external monitoring. Or they could allow scientists to control brains with light without needing bulky optical fibers.

Cutting the cord is just the first step to fine-tuning neurological treatments—or enhancements—to the tune of your own brain, and 2019 will keep on bringing the music.

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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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#433828 Using Big Data to Give Patients Control ...

Big data, personalized medicine, artificial intelligence. String these three buzzphrases together, and what do you have?

A system that may revolutionize the future of healthcare, by bringing sophisticated health data directly to patients for them to ponder, digest, and act upon—and potentially stop diseases in their tracks.

At Singularity University’s Exponential Medicine conference in San Diego this week, Dr. Ran Balicer, director of the Clalit Research Institute in Israel, painted a futuristic picture of how big data can merge with personalized healthcare into an app-based system in which the patient is in control.

Dr. Ran Balicer at Exponential Medicine
Picture this: instead of going to a physician with your ailments, your doctor calls you with some bad news: “Within six hours, you’re going to have a heart attack. So why don’t you come into the clinic and we can fix that.” Crisis averted.

Following the treatment, you’re at home monitoring your biomarkers, lab test results, and other health information through an app with a clean, beautiful user interface. Within the app, you can observe how various health-influencing life habits—smoking, drinking, insufficient sleep—influence your chance of future cardiovascular disease risks by toggling their levels up or down.

There’s more: you can also set a health goal within the app—for example, stop smoking—which automatically informs your physician. The app will then suggest pharmaceuticals to help you ditch the nicotine and automatically sends the prescription to your local drug store. You’ll also immediately find a list of nearby support groups that can help you reach your health goal.

With this hefty dose of AI, you’re in charge of your health—in fact, probably more so than under current healthcare systems.

Sound fantastical? In fact, this type of preemptive care is already being provided in some countries, including Israel, at a massive scale, said Balicer. By mining datasets with deep learning and other powerful AI tools, we can predict the future—and put it into the hands of patients.

The Israeli Advantage
In order to apply big data approaches to medicine, you first need a giant database.

Israel is ahead of the game in this regard. With decades of electronic health records aggregated within a central warehouse, Israel offers a wealth of health-related data on the scale of millions of people and billions of data points. The data is incredibly multiplex, covering lab tests, drugs, hospital admissions, medical procedures, and more.

One of Balicer’s early successes was an algorithm that predicts diabetes, which allowed the team to notify physicians to target their care. Clalit has also been busy digging into data that predicts winter pneumonia, osteoporosis, and a long list of other preventable diseases.

So far, Balicer’s predictive health system has only been tested on a pilot group of patients, but he is expecting to roll out the platform to all patients in the database in the next few months.

Truly Personalized Medicine
To Balicer, whatever a machine can do better, it should be welcomed to do. AI diagnosticians have already enjoyed plenty of successes—but their collaboration remains mostly with physicians, at a point in time when the patient is already ill.

A particularly powerful use of AI in medicine is to bring insights and trends directly to the patient, such that they can take control over their own health and medical care.

For example, take the problem of tailored drug dosing. Current drug doses are based on average results conducted during clinical trials—the dosing is not tailored for any specific patient’s genetic and health makeup. But what if a doctor had already seen millions of other patients similar to your case, and could generate dosing recommendations more relevant to you based on that particular group of patients?

Such personalized recommendations are beyond the ability of any single human doctor. But with the help of AI, which can quickly process massive datasets to find similarities, doctors may soon be able to prescribe individually-tailored medications.

Tailored treatment doesn’t stop there. Another issue with pharmaceuticals and treatment regimes is that they often come with side effects: potentially health-threatening reactions that may, or may not, happen to you based on your biometrics.

Back in 2017, the New England Journal of Medicine launched the SPRINT Data Analysis Challenge, which urged physicians and data analysts to identify novel clinical findings using shared clinical trial data.

Working with Dr. Noa Dagan at the Clalit Research Institute, Balicer and team developed an algorithm that recommends whether or not a patient receives a particularly intensive treatment regime for hypertension.

Rather than simply looking at one outcome—normalized blood pressure—the algorithm takes into account an individual’s specific characteristics, laying out the treatment’s predicted benefits and harms for a particular patient.

“We built thousands of models for each patient to comprehensively understand the impact of the treatment for the individual; for example, a reduced risk for stroke and cardiovascular-related deaths could be accompanied by an increase in serious renal failure,” said Balicer. “This approach allows a truly personalized balance—allowing patients and their physicians to ultimately decide if the risks of the treatment are worth the benefits.”

This is already personalized medicine at its finest. But Balicer didn’t stop there.

We are not the sum of our biologics and medical stats, he said. A truly personalized approach needs to take a patient’s needs and goals and the sacrifices and tradeoffs they’re willing to make into account, rather than having the physician make decisions for them.

Balicer’s preventative system adds this layer of complexity by giving weights to different outcomes based on patients’ input of their own health goals. Rather than blindly following big data, the system holistically integrates the patient’s opinion to make recommendations.

Balicer’s system is just one example of how AI can truly transform personalized health care. The next big challenge is to work with physicians to further optimize these systems, in a way that doctors can easily integrate them into their workflow and embrace the technology.

“Health systems will not be replaced by algorithms, rest assured,” concluded Balicer, “but health systems that don’t use algorithms will be replaced by those that do.”

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#433521 Humanoid robot dental “practice ...

No more inept dental trainees practising on a very reluctant and – quite likely – horrified human “volunteer”. This Simroid dental training humanoid robot will take one for the team with a smile (or what’s left of it)! Related PostsAn … Continue reading

Posted in Human Robots