Uncertain Health in an Insecure World – 71

“Before I Get Old”

In My Generation (1965), The Who protested that their parents were holding them back. “Hope I Die Before I Get Old” was the youthful Pete Townshend’s lament against the ravages of time. 

Pete is now 70 years old.

In their parents’ era, BBC Radio listeners heard poet Dylan Thomas’ read Do Not Go Gentle Into That Good Night. Thomas chided his father to fight on, despite the old man’s life being filled with disease and pain. “Old age should burn and rave at the close of day…Rage, Rage against the dying of the light”, even if the next day brings suffering. In the sci-fi movie Interstellar (2014), Professor John Brand (played by Michael Caine, age 82) repeated this line as the world urged NASA astronauts into the abyss of space on a vain mission to save struggling humankind.

Life expectancy at birth (LEB) is a statistic applicable to all living organisms – man, animals and plants.

LEB is an actuarial measure of an organism’s expected survival in the face of evolution, innate host defenses and lifestyle. Whether humans, opossums or guppies are involved, greater predation and accidental death lessens the impact of natural selection on increased life span.  Externally imposed caloric restriction and intrinsically lower basal metabolic rates are also known to lengthen lifespans – just ask any 190 year old Galapagos giant tortoise, or 405 year old Arctic Ocean quahog clam!

In the Bronze Age (3,000 – 1,200 B.C., left) and Iron Age (1,200 – 550 B.C., right), human LEB was just 26 years. Over thousands of intervening years, world-wide LEB doubled to 52 years for those born in 1960-65.  For the 2010-2015 birth cohort, LEB increased to 71 years. Ceteris paribus, current projections are that LEB will rise to 75 years by 2040-45. 

Doing the math, LEB gained +0.38 years per year over the prior 50 years, but will grow by only +0.13 years per year over the next 30 years. If the human genome remains largely stable, then this apparent blunting of the LEB curve (below) must be due to putative externalities – accidental deaths, predation (i.e., wars, genocides), excessive caloric intake (i.e., diabetes), and/or global environmental decline.

For rockers, life has an especially poor prognosis.

The Who drummer, Keith Moon (above), died at age 32; it was not a natural death. A 2012 British Medical Journal study sampled 1,489 rock and pop stars from 1956 and 2006, and showed that 9% died prematurely, largely as a result of substance abuse tied to psychic trauma from adverse childhood experiences (ACE).

Evolution tinkers very slowly with the human genome.

The best kept Human Genome Project (2000) secret is that differences in our genes’ DNA explain very little of why most of the lethal chronic mental and physical diseases occur – 5-10% at most!! In his January 5, 2016 blog, National Institutes of Health chief Francis Collins (age 65) reflected back on 2015’s scientific breakthroughs, highlighting the CRISPR/Cas9 gene-editing technique – Science magazine’s breakthrough of the year. “Like a scalpel”, CRISPR (below) uses an RNA segment attached to an enzyme to seek out and cut a short DNA sequence from the genome. This so-called ‘gene drive’ can re-engineer an organism’s genome, intentionally spreading a trait through a population much faster than Mendelian inheritance. Recently, Chinese scientists have used CRISPR to edit germ line cells in human embryos, edging up to the ethical red-line of engineering human life.

There are good natural selection reasons, seemingly perverse, for the preservation of mixed bag genes.

For example, the APO E4 gene located on the long arm of chromosome 19 at position 13.2 (i.e., locus 19q13.2, above) has three apolipoprotein E alleles – e2, e3 and e4 – which produce three different proteins that combine with lipids like cholesterol. More than 50% of the world’s population owns the benign ‘e3’ haplotype. But the ‘e2’version carries the risk of hyperlipoproteinemia type III, which increases the risk of atherosclerotic heart disease and stroke.  The ‘e4’ version increases the risk of late-onset Alzheimer’s disease and age-related macular degeneration.

Teleologically speaking, it could be argued that these diseases of aging are emerging now as the elderly population expands, while they were relatively rare occurrences earlier in human evolution.

 

Like evolution, genome-modifying research successes come slowly.

It is becoming abundantly clear that our capacity to sequence and snip genes remains a pale imitation of the natural evolution of the genome. The massive quantity of big data from genetic research initiatives continues to challenge scientists. Memorial Sloan Kettering Cancer Center’s global Project GENIE database has accrued 17,000 patient records awaiting decryption. We know that characterizing genomic mutations in tumors leads to precision medicine insights that inform clinical decision-making regarding existing drug treatment and new drug development (see Post #65). But computational challenges implicit to Project GENIE’s big datasets require big bioinformatics partners like Sage Bionetworks.

Of course, Facebook isn’t standing idly by watching the others.

At the University of Michigan, researchers have developed a Facebook app called Genes for Good, to support a genetic testing initiative that links ancestral genetic data to the daily health habits of study participants. In 2015, of the 8,310 would-be participants (below) who used the app, only 3,702 were eligible for submitting a study spit kit. Once privacy issues are managed, in 2016, the participants will receive their raw genetic data in a manageable format. Who knows what, if any, insights this information will provide to those enrolled?

In a 1989 ABC Good Morning America interview, Pete Townshend confessed that when writing the lyrics to My Generation, while riding on a train, his meaning for “old” was actually “very rich.”

There are some who believe that many nouveau riche high-tech billionaires are investing in genome manipulating precision medicine technologies to forestall their own mortality. Mark Zucherberg is 31, Travis Kalanick is 39, Sergey Brin is 42, Jeff Bezos is 51 and Bill Gates is 60.

Perhaps The Who was being prescient when Pete conflated the “old” and the “very rich”, in an era before the rise of potential LEB-adding gene-modifying technologies.

Facing it squarely, it's 2016, and we in the Square are all aging.

But before we get old, let's explore this uncharted space quadrant, and “Rage, rage against the dying of the light…”  

Uncertain Health in an Insecure World – 70

“So What?”

Throughout 2015, a Microsoft Cloud ad touted the world-wide connectivity of some 450 million fanatics to Real Madrid football, positing that “It is not the device that is mobile… It is You!”

“So what?” is the Real question.

On the threshold of 2016, an idea remains pervasive that good health is a gift of better healthcare. In truth “It’s not the system of care that brings health… It is You!”

“So what?” is it that keeps humankind trapped in the era of imprecision medicine.

Despite technology triumphs and access upgrades, most patients still fly blind through a flawed healthcare system. This is partly because the experience dis-empowers patients and dis-intermediates physicians.

 “So what?” can be done to connect purported innovations with perceived needs.

Modern medicine’s current whack-a-mole approach to disease detection is wasteful. For example, the cost of false-positive mammograms performed on American women exceeds >US$4B per year!! Could this have anything to do with the huge number of imaging sites offering this basic diagnostic service?

Generalist physicians often function like epidemiologists. Their point-of-care clinical decisions can be enhanced by simply adding one or two data points. For example, public health information about the local prevalence of beta-hemolytic strep cultures and antibiotic prescribing patterns could reduce defensive medicine’s sore throat over-treatment bias, and the rise in drug resistance.

Specialist physicians frequently apply aggregated randomized clinical trial (RCT) and registry data to patient care. Unfortunately, many patients just don’t respond. Despite statistically significant data showing a cohort treatment’s benefit, averaged RCT responses are not a great predictor of individual patient responses.

“So what?” can be done. Views vary…

Enter two experts.

Michael Porter and Thomas Lee have proposed a new strategy to “fix” struggling healthcare systems around the world (Harvard Business Review, October 2013). They suggest a laser-like focus on the needs of the patient, and more rational service delivery in the right locations. They warn that there are no “magic bullet” solutions to the systemic problems and entrenched forces negatively impacting healthcare value for patients.

The lack of precision in the maintenance of wellness is even more shocking.

Enter one visionary.

Leroy (Lee) Hood founded the Institute for Systems Biology in 2000, when he and others at the University of Washington became convinced that RCT’s alone could not reflect the complexity of individual disease biology. Their novel P4 paradigm – Predictive, Preventive, Personalized and Participatory – aggregates billions of human data points in the Cloud, reflecting the genomic and environmental factors characterizing illness and wellness at the organismic level.

Of note, the genetic risk of illness is not a disease state.

But if early-onset Alzheimer’s risk can be identified before the transition from organismic illness into clinical disease, an intervention to delay the onset could be very useful. For example, in early prion brain disease, arachidonic acid metabolic and calcium signaling changes in the glutamate receptor ionotropic N-methyl D-aspartate 1 (GRIN 1) protein superfamily (below) might offer interventional targets.

A new age registry study – the 100K Person Wellness Project – has been underway in Seattle Washington since 2014. So far, one hundred and seven “well pioneers” have had their genomes sequenced, and their gut microbiome, clinical, proteomic, metabolomic, and Fitbit gyroscopic little data moved to the Cloud. Up there, 107 ‘N=1’ dense data experiments have yielded >35,000 correlations designed to establish each individual’s genetic risk for sixty diseases. Resulting high- or low-risk genetic probability markers have revealed several actionable possibilities. Wellness coaching opportunities to encourage personal behavior changes were available for 70% of this cohort. For example, when hemochromatosis homozygous subjects with arthritis proactively pursued weekly blood drawing, they were restored back to normal health (i.e., wellness).

That’s “So what!” These well pioneers actually took back control of their individual health!

In order to more widely apply P4 approaches, new technologies are needed. These include 3^rd generation DNA sequencing (cheaper, faster), peptide protein capture agents (for ELISA assays on micro-sized blood samples), dynamic personalized data (individualized Clouds), selected reaction monitoring (SRM) assays for targeting blood proteins (reflecting specific cellular network perturbations in lung cancer, PTSD, etc.), and single instrument multiplex diagnostics for micro RNA’s and RNA sequencing (based on existing scientific evidence).  

     

Some companion diagnostics are now available for home use. But patients still have to go to the doctor for treatment.

“So what?”, then, is the value of all this testing… to You?

Real value lies in information collected and modeled being actionable at an individual level.

We in the Square begin 2016 full of hope, but with many unresolved “So what?” questions. 

Uncertain Health in an Insecure World – 69

“War is Over?”

When John Lennon and Yoko Ono released Happy Xmas (War is Over) in December 1971, the song was both inspirational, and aspirational. The Harlem Community Choir sang back up to lyrics set to the traditional English ballad, Skewball. In the pre-social media era, Lennon had learned the hard way how to do political and social advocacy. “Now I understand what you have to do – Put your message across with a little honey.”

“So this is Christmas (2015), and what have you done?”

And in Syria, war isn’t over.

Of the 12 million refugees displaced inside Syria or fleeing that morass, half are less than 18 years old, and 40% are children under the age of 12. Nearly 80% of these child refugees have experienced a death in the family, 60% have seen someone beaten or shot, and 30% have been kicked, shot at or physically hurt. Some 12,000 children have died since 2011. But it’s the emotional trauma that endures, with PTSD levels 10-times the prevalence among other children around the world. The resulting mental health sequelae will follow them whatever country of asylum they reach.

Many organizations and countries have done something.

Save the Children, UNHCR, UNICEF, USAID, and 30+ other governmental, non-governmental and religious agencies are all doing their level best to respond to the Syrian refugee crisis. Children “living” in makeshift camps suffer from illnesses like diarrhea and cholera, malnutrition and abuse. Many are exploited as fighters, human shields or non-combatant supporters. With another bitter winter coming to the region, for these poorly clothed children, things will only get worse.

     

Jesus Christ was born 10 miles south of Jerusalem, in Bethlehem, just 140 miles from Damascus.

On March 4, 1966, John Lennon casually commented to British journalist Maureen Cleave that, “We’re more popular than Jesus now.” And while the 24 year-old Beatle noted that “Jesus was all right”, he also predicted that “Christianity will go.” Unlike some blatantly unapologetic Christian U.S. politicians making ISIS fear-infused hateful statements about Muslims, John and Beatles manager Brian Epstein had to eat the proverbial carpet of apology.

Barrel bombs dropped from Syrian army helicopters kill more civilians than ISIS (above).

Fear of these airborne attacks in al-Assad opposition neighborhoods has fueled this largest human exodus since World War II. In the view of Kenneth Roth, Human Rights Watch executive director, this governmental terrorism of the Syrian population, “Is a recruitment bonanza for ISIS because the group can claim to be standing up to these atrocities.” The global community has lined up against or with the al-Assad regime. The European Union talks about addressing the mysterious “root causes” of migration to Europe, while remaining largely passive. Also seemingly impotent, the UN Security Council has repeatedly called for an end to “indiscriminant employment of weapons in populated areas… such as the use of barrel bombs.”

With Russia, Iran continues to back the al-Assad regime, making these war crimes possible.

Two millennia ago, three wise men traveled from the East to worship one newborn King of the Jews. Balthasar, Melchior and Gaspar were from ancient Persia, now modern Iran. After the origination of Christianity among Jewish Aramaic-speaking Semitic peoples of Judah (Israel, Palestine and Jordan), it quickly spread through modern day Syria, Lebanon, Iraq, Iran and Turkey. From there, like modern refugees (below), Christianity migrated into Greece, Armenia, Georgia, the Caucasus and the Balkans.

Syriac Christianity, centered in Antioch and along the eastern Mediterranean coast – the Levant – believes there were as many as twelve wise Magi!

This small part of our little blue orb, known in Arabic as al-Sham (the Sh in Da’esh), is now part of the Islamic State of Iraq and the Levant (ISIL).

The Levant has long been a hotbed of religious strife, whatever we’ve called the area.

In the Levant, despite many wise men and well-meaning saviors, there’s always something deadly happening to create martyrs.

But children... Seriously? 

Reflecting on 2015's uncertain health in an insecure world, we and those walking with us in the Square from around the world still aspire to…

“A very merry Christmas and a happy New Year,

Let’s hope it’s a good one without any fear.”

Uncertain Health in an Insecure World – 68

“Reprieve”

Eric Clapton’s I Shot The Sheriff refrain, “One day the bottom will drop out…”,  brings to mind the finality of irrevocable acts.

The World tells us when enough is enough, in its own, none too subtle ways. Unfortunately, the hardest thing to do, beyond listening, is to actually hear what it is saying.

The World does not speak our 6,500 languages… any of them. It talks to us in tongues. We translate with numbers that humans can measure – vital signs, of a sort – air temperature, sea level, ozone depletion, red tides, epidemics, droughts and deaths.

During this week’s global climate summit in Paris (COP21), delegates from 196 countries who have been listening hard for what seems like too many years (since the Kyoto Protocol of 1997), many of the same people who fumbled at Copenhagen in 2009, finally spoke… as one. Their final agreement on curbing fossil fuel use is designed to restrain the rise in average global temperature to “well below” +2 degrees Celsius above pre-industrial levels (or +3.6 degrees Fahrenheit in the one country still using that scale).

In Obamacare terms, this warming projection is like “bending the curve” of cost expenditures in order to achieve healthcare system sustainability. As noted by U.S. President Barack Obama, the Paris plan is “a turning point for the world… the best chance we have to save the one planet that we’ve got.”

How does one translate these temperature targets into global ecosystem terms?

Big data driven predictive analytic models have shown that between 2050 and 2100, the Paris accord’s limits on greenhouse gas emissions will achieve a new equilibrium – when trees, soil and oceans can naturally absorb what human activity is generating. John Schellnhuber of Germany’s Potsdam Institute for Climate Research calls this positive tipping point “net zero.”

The top greenhouse gas-emitters – China, U.S., EU, India, Russia, Indonesia, Brazil and Japan – made 2030 pledges to shift from carbon-intensive fuels in favor of renewable energy sources such as wind and solar.

Of course, countries can view this multi-trillion dollar drive to reduce emissions very differently. China, for example, is in the midst of its own post-industrial revolution. China is also the #1 carbon-based fuel user, at 2,972 millions of metric tons of oil equivalents, generating 66% of its energy from coal burning (below).

Beijing, a city of 20 million souls, spent most of the past week under a red alert due to extremely high particulate level smog. Widespread industrial coal burning causes poor air quality in China’s cities on a regular basis, but last week’s levels were an “Airpocalypse.” The handshake with the Devil made by the Chinese Communist Party in return for breakneck economic growth is paying negative ecologic returns. 

What does the bottom falling out look like?

By the year 2100, the United Nations Intergovernmental Panel on Climate Change (IPCC, est. 1988) estimates a 20 inch sea level rise. Expert opinions differ on these numbers – the U.S. National Academy of Sciences (est. 1863) predicts a rise ranging from 16 to 56 inches, depending on how we humans listen and respond to Earth’s queues. According to scientists and journalists at Climate Central (est. 2008), including some Weather Channel veterans, this places some 280 million peoples’ houses at risk of becoming submerged.

The U.S. Environmental Protection Agency (EPA, est. 1970) says that ocean levels have already risen 8 inches since Europe’s Industrial Revolution, circa 1870. Pacific islands like Nauru in the Marshall archipelago (above) and many other vulnerable countries are threatened right now. Bangladeshi farmers have created floating agricultural rafts from straw, rice stubble and water hyacinth in response to ever worsening flooding.

As Unilever CEO, Paul Polman stated from Paris, “This agreement establishes a clear path to de-carbonize the global economy within the lifetimes of many people alive today.” Outside the boardrooms, protesters in the streets are angered by all the misdirection and obfuscation.

Oddly, the new accord waits until 2020 to take effect, largely so that individual governments – in some 55 countries representing at least 55% of global emissions – can ratify and enact the required standards. The intersection of policy and politics is jobs, and it would be naive to imagine that economies won’t fail and governments won’t fall in pursuit of these Paris ideals.   

We will not dwell on the obvious adverse effects of this carbon fuel cataclysm on human health.

The U.S. Centers for Disease Control and Prevention (CDC, est. 1946) National Center for Environmental Health has surveyed the scientific literature on climate change, together with other natural and human-made stressors http://www.globalchange.gov/engage/activities-products/NCA3/technical-inputs The threats to human health and promotion of disease are diverse and patently evident (below), and appear to be intensifying, even in the less extreme North American ecosystem. New public health problems are to be expected from climate-induced disruptions of physical, biological and ecological systems.

 

Guitar aficionados have nick-named Eric Clapton ‘Slowhand’, because he plays complex rock riffs with such relaxed ease. In his rock classic, The Crossroads, Clapton sings, “I went down to the crossroads, fell down on my knees.”

The World is squarely at The Crossroads, right now!

After decades of analytic complexity from scientists and perilous advocacy by activists, COP21 looked too easy. Those who have brought Mother Earth to its knees have been handed one final chance… A reprieve.

Many of us standing in the Square today won’t be here in 2050.

But as the seas rise and cities choke, from this day forward, we are all out of envelopes to tear, and others to blame.