Thursday, August 27, 2015

Uncertain Health in an Insecure World – 54


When a cardiac patient suddenly loses their vital signs, as their pulse or breathing stops, doctors call it "crashing". The medical team’s response to the critical situation must be swift and decisive, if the patient is to survive. And even then, the outcome is always in doubt.

This week saw the crash of global stock markets… oddly named a “correction”. This week saw crude oil prices drop below US$40 per barrel. This week saw reports of a 165o F heat index in Iran, and of the hottest July on record in the U.S. since 1880, averaging 0.85o C above the 20th century average.

My question is simple. What does this all mean for global health?

We have previously explored the interconnectedness of economic and environmental hits on the health of people around the world.  People are displaced as food supplies dwindle in the face of drought. Medicines are misappropriated by war and corruption. Killer epidemics emerge from the depths of jungles. Epigenome and microbiome cell milieus shift in response to water and air borne toxins. And lifestyle-driven obesity adds to chronic disease prevalence.

These slow moving, inexorable adverse trends are constantly shifting the tectonic plates of global health. But when a sudden worldwide earthquake hits, what are the short and longer term sequelae?

Life has a poor prognosis. And nobody can predict the future… of markets, the weather, natural resources and viral mutations.

History repeats itself. Can we learn from the past, and use past experiences to shape the future?

The last time the price of a barrel of crude oil fell below US$30 per barrel was 1986. That year, the global oil glut drove the average price down to US$26.80 a barrel. That year, the world’s population was only 4.9B and the average life expectancy in the U.S. was 74.7 years. The U.S. space shuttle program was put on hold after the Challenger blew up off Cape Canaveral; the average age of the crew was 40.1 years.

That year in the U.S., the violent crime rate rose to 54.8 per 1,000 population. The Congress passed an immigration bill preventing the hiring of illegal aliens. Back then, there was no U.S. presidential candidate/reality TV magnate connecting the two.

Before the global economy was declared “flat” by author Tom Friedman, the world had begun to think of itself in global terms. The best picture of the year went to Out of Africa, and the number one hit record was We are the World (USA for Africa).

What kind of health was the world experiencing in 1986?

In the U.S., the FDA approved the first genetically engineered vaccine for Hepatitis B. The CDC reported that the year’s H1/N1 Influenza strain originated in North China, beginning a global Asian flu epidemic. In the then Soviet Union, the Chernobyl nuclear reactor core melted down, radiation poisoning thousands for generations (below, left). In Bhopal India, Union Carbide agreed to settle with thousands of toxic gassing victims (below, right). 

Rita Levi-Montalcini and Stanley Cohen received the Nobel Prize in Medicine & Physiology for describing how neural growth factor (NGF) and epidermal growth factor (EGF) regulate cell growth and differentiation, opening a new era of research into dementia, wound repair and cancer.

Nearly thirty years have passed. Nothing and everything have changed.

The globe is now hotter, flatter and more crowded.

The world is telling us something. The patient is crashing.

Like you, we in the Square are white-knuckling it. But by learning hard lessons from what history teaches, we can rally before hitting bottom.  

Tuesday, August 18, 2015

Uncertain Health in an Insecure World – 53

“Handling the Truth”

Earlier this month, posted a story on social media about the FDA’s July 31, 2015 approval of a “New Heroin-based Vaccine (That) Could Eradicate Chickenpox Disease” in children. The ring of truth led to hundreds of Facebook likes and Twitter re-tweets.

In the article, Bob Flanagan quoted Dr. Yu Shi Jung (below) as saying, “Heroin tends to attach to the chickenpox virus which stimulates the body’s immune system to recognize the agent as a threat and destroys unwanted microorganisms.”

Dr. Jung’s affiliation was not listed.

In response to the news, an indignant Association for a Vaccine-free America spokesperson immediately asked, “Why would I inject my children with heroin to get rid of such an insignificant disease as chickenpox?” Why indeed? Other commenters quickly confirmed that chickenpox was rarely fatal.

Of course, this story was completely bogus, one of many generated by hoaxers at

Those using social media are bombarded with unfiltered information from friends and followers. While vouched truthful by the originators, it need not be believed.

In fact, on the same day, the FDA did approve an Emergency Use Authorization (EUA) for the OraQuick™ Ebola Rapid Antigen Test for point-of-care detection of the Ebola Zaire Virus in symptomatic patients, as an alternative to slower but more sensitive viral nucleic acid testing. A letter of authorization is available on the official FDA website.

On CNN’s Reliable Sources show this week, TV and radio personality Michael Smerconish warned that the distinction between news and entertainment is growing blurry, and that viewers should not confuse the two. This, on the same day that news outlets like CNN were giving Donald Trump ten times more coverage than any other Republican 2016 U.S. presidential candidate.  This, in the same month that Jon Stewart signed off from his final The Daily Show, after sixteen years of admired newsy satire.

Social media and CNN coverage share the same 24/7 real time pressure to create content. The quality of that quantity can be questioned, and is often questionable. Fortunately, scientific and medical information sharing does not follow the news cycle. As a result of deliberate peer review, there is less chance of short-cycle harmful information becoming actionable.

Finding the truth takes time, and effort.

On the other hand completely, this month we celebrate the ninth anniversary of the 2006 coining of the term “cloud computing” by Google’s Eric Schmidt (above). My on-line non-Wikipedia sourced research has also determined that the term “cloud” was first quoted in a figure (below) published by MIT internet scientists Sharon Gillett and Mitchell Kapor. Those using the term daily should probably read their prescient 1997 scholarly paper at  

It must be true, because I tweeted about it yesterday!

Have you ever wondered about the origins of words like “biotechnology” and “business-to-business (B2B) internet”? When a start-up seeks financing through the issuance of shares in an initial public offering (IPO) in the U.S., the Securities Act of 1933 kicks in. For investors to be assured “full and fair” disclosure of what the NewCo. makes, idiosyncratic ideas and language must be translated by marketing firms into non-technical wording that can be understood by people not working in the business. Being labeled a “biotechnology” or “B2B” start-up adds legitimacy, and renders the NewCo. part of an analogous business model in a comparable business sector.

When these and other terms are hash-tagged (#) on social media, they become metadata connects to similar themes and content. The term “hash tag” was first used in a blog post by Stowe Boyd on August 26, 2007 (“Hash Tags = Twitter Groupings”). This Twitter tool and robotic trending analytics are the basis for social media marketing influencers moving products and services.

The Truth, not Trump truisms or bot re-tweets or the 2005 Steven Colbert Report’s truthiness (“feels right in the gut…” without confounding logic or facts), is hard to find and often harder to handle.

Valid information must be actively sought.

Easily accessed content should be handled with great care. 

We in the Square know that the difference matters. When civilization ends, it might just be at the speed of the #internet.

Tuesday, August 11, 2015

Uncertain Health in an Insecure World – 52


“When the whole world is silent, even one voice becomes powerful.”
Malala Yousafzai (2014 Nobel Peace Prize)

When Frances Kathleen Oldham applied for a pharmacology lab position in 1935, University of Chicago Professor Eugene Geiling offered “Mr. Oldham” the job without an interview. Her McGill University training was top notch, and she was encouraged by her mentor to accept the offer. Last week, “Miss Oldham” (below), died in London Ontario with her family beside her at age 101.

She lived a long life, a moral life, mostly in obscurity.

As the U.S. Food & Drug Administration (FDA) medical officer in the 1960's, Dr. Frances Kathleen Kelsey (since married) received the William S. Merrell Company of Cincinnati request to market thalidomide in the U.S. The drug, called Kevadon™, was portrayed as a miracle cure for morning sickness of pregnancy, an indication for which it had been approved in nearly fifty countries since its introduction by Germany’s Chemie GrĂ¼nenthal in 1957. On this basis, Merrell Co. expected a routine review and rubber stamp approval.

Dr. Kelsey, a serious scientist, had serious reservations.

Her opposition to thalidomide made her a target of company lobbying and complaints to her FDA superiors. Probing questions about the drug’s safety delayed FDA actions until 1961, when a German researcher found a link to serious newborn lung and limb malformation defects (phocomelia, see below), and in utero deaths. Over 10,000 cases were reported worldwide, mostly in Europe, Britain, Canada and the Middle East, of which only 50% survived beyond childhood. 

For her courage in defense of human health under pharmaceutical company fire, in 1962 President John F. Kennedy presented Dr. Kelsey with the highest U.S. award for civilian service at a White House ceremony (below). The U.S. Congress passed legislation, signed by President Kennedy, requiring drug makers to prove that new drugs were safe and effective before marketing. Dr. Kelsey was put in charge of FDA's new drug safety branch in 1962; she had a distinguished 45 year career.

Thanks to Dr. Kelsey, thousands lived and avoided suffering.

Remarkably, thalidomide is still sold globally by Celgene as an immune-modulator drug for the treatment of non-pregnant patients with multiple myeloma (FDA approved in 2006, Australia TGA approved in 2009, EU EMA approved in 2008), HIV-associated Kaposi sarcoma & wasting, Crohn’s disease, and skin complications of leprosy (FDA approved in 1998, TGA approved in 2009).  Modern immuno-therapies are likely to signal an end to thalidomide therapy in the developed world by 2020, but its use in the developing world will continue. 

Dr. Kelsey’s work gave birth to the modern era of pharmaco-vigilance (PV). 

PV is defined by the World Health Organization (WHO) as the pharmacologic science and activities related to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problems. Over 100 countries have committed to WHO’s International Drug Monitoring Programme, contributing information to an international database. As specified by the EU definition of PV, the emphasis is monitoring and related actions to mitigate the drug’s potential for post-marketing adverse impact on public health.  Such pro-active risk management includes post-release regulatory actions (i.e., additional labeling) by the FDA, European Medicines Agency (EMA), etc.

Given the dire consequences of laxity, a large PV industry sector has naturally emerged.

Others responsible for effective PV include patients, healthcare providers, pharmaceutical companies and drug importers. Large pharma companies and medical device makers are required to carry out post-marketing surveillance (PMS; a.k.a. Phase-4 trials) for years following regulatory approval. FDA’s Adverse Event Reporting System (FAERS) is a central database designed to monitor and analyze reported adverse events and poisonings. FDA’s MedWatch Program website is designed for healthcare professionals and the public to report reactions to drugs & devices, which are entered into the FAERS database.

Medication distributors have established subsidiaries (i.e., Express Scripts’ UBC) dedicated to PV functions. Clinical research organizations like Parexel include PV in their menu of CRO services. Specialty firms (i.e., Clinquest, Prosar) perform post-marketing PV for drugs and devices throughout product life cycles. The PV sector now sponsors international journals, professional societies and scientific sessions.

Last week’s FDA approval of a highly porous anti-epilepsy drug delivery system made using 3D printing (Aprecia’s Spritam, above) is a good example of the high tech and biotechnology that regulatory agencies must now evaluate before and be vigilant about long after marketing begins. 

Fifty-three years later after being honored by JFK, on the day before her death, Dr. Kelsey received the Order of Canada. In March of 2015, 126 surviving Canadian thalidomide victims received $125,000 each from the Canadian government. Daughter Christine Kelsey reflected back on “Frankie’s” early life in a 2010 New York Times article, saying “When a woman took a job in those days, she was made to feel as if she was depriving a man of the ability to support his wife and child.”

Thanks to “Frankie” and others, women have come a long way in science and medicine.

While important and hard, there is little heroic about pharmaco-vigilance.

We in the Square profess that personal heroism is lonely, often occurring before the organized world requires it. 

Tuesday, August 4, 2015

Uncertain Health in an Insecure World – 51

“The Monsanto Years”

One need not be a Rock & Roll Hall of Famer to have a cause.

For Neil Young, The Monsanto Years began in 1972 when his first son Zeke was born with neurological damage from an in utero stroke. His second son Ben was born in 1978 with cerebral palsy and quadriplegia. His dad, Scott Young (below), a famous hockey writer, died in 2005 from Alzheimer’s disease. His 2015 album of this name is a musical rant against the multi-national agrochemical & biotechnology corporations, whose products increase crop yields but negatively impact human health through the food chain.

Countries too can have a cause.

The Netherlands has just joined nations as different as Russia and Mexico in saying “No!” to Monsanto’s sale of glyphosate-based herbicides (RoundUp™) for non-commercial use. So, while Dutch lawn growers and home gardeners will now have to fend for themselves, the big agribusinesses are still free to use herbicides linked by environmental health research to an array of birth defects, neurological conditions and kidney diseases (focused in Sri Lanka). The World Health Organization recently reported that glyphosates can also cause cancer, promoting the May “March Against Monsanto” and genetically modified (GMO) foodstuffs by hundreds of thousands in 38 countries around the world.

Systems biologists know that you need not understand every step to know that something works.

The major impact of glyphosates on the human body is via the cytochrome P450 (CYP) metabolic pathway, a family of enzymes that detoxify ingested substances, control medication metabolism and regulate other ubiquitous cell functions. CYP alters amino acid tryptophan levels and serotonin neurotransmitter signaling, which may in turn worsen Alzheimer’s and Parkinson’s disease. CYP changes may also cause endocrine disorders and weight gain. Industry studies submitted to the E.U. Commission underplayed the relationship between RoundUp™ and birth defects (i.e., teratogenicity).
Conspiracy theorists surround this issue.

WikiLeak has released reports of the Bush 43 Administration’s State Department plans to “retaliate and cause pain” against “target countries” in Africa, Europe and Latin America that refused to use GMO seeds. The U.S. also lobbied foreign governments to adopt pro-agriculture biotech policies, permissively regulate GMO seed use, and oppose genetically engineered (GE) food labeling.
Scientific literature on this subject is spotty.

The Journal of Biomedical Research International (impact factor 1.58) recently published a study showing that Monsanto’s undisclosed adjuvants in RoundUp™ are up to one thousand times more toxic than the main active ingredient, glyphosate. In 2007, The U.S. Geological Survey reported glyphosate and its breakdown products entered the air, fell to Earth in rain, and permeated ground water in Mississippi, where 2 million kilograms of the stuff is applied annually. Not surprisingly, these toxins are reported by the on-line Journal of Environmenal & Analytical Toxicology (impact factor unavailable) to be measurable in the urine of European animals and humans, entering waste water through that pathway.

Often, it’s all quite personal.

An equal opportunity activist, Young also critiqued Starbucks, Chevron and Walmart for various compounding corporate sins. Their responses reflect an alternate view of a complex, multifaceted issue.

Waging heavy peace against a powerful force takes courage and persistence.

Presenting an alternate view of the world, as a person or proselyte, requires passion.

Neil Young’s song, Ohio, told of four unjust deaths in 1970 at the hands of the U.S. National Guard. It was a bald brutal fact. If millions are dying from RoundUp™ toxicity in The Monsanto Years, then those facts should be equally incontrovertible.

Problems arise when governments squelch data, and when advocates base their case on weak science.
In the Square, we seek the truth. In the Square, we are moved by real passion and robust science. 

On this issue, we await the emergence of both.