The impact of the last snowflake

Was the recent Swiss avalanche’s cause the last, triggering snowflake, or the billions of snowflakes before it?

There’s been a slight increase in the number of PNAS studies that included the “catastrophic” search word from October 2016 to mid-January 2018 compared to the January 2014 to mid-April 2015 period referenced in How well can catastrophes be predicted?.

What are the drivers?

Or is the main driver something else?

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Non-CpG DNA methylation

This 2017 Korean review compared and contrasted CpG and non-CpG DNA methylation:

“Non-CpG methylation is restricted to specific cell types, such as pluripotent stem cells, oocytes, neurons, and glial cells..accumulation of methylation at non-CpG sites and CpG sites in neurons seems to be involved in development and disease etiology.

Non-CpG methylation is established during postnatal development of the hippocampus and its levels increase over time. Similarly, non-CpG methylation is scarcely detected in human fetal frontal cortex, but is dramatically increased in later life. This increase in non-CpG methylation occurs simultaneously with synaptic development and increases in synaptic density.

In contrast, CpG methylation occurs during early development and does not increase over time.

Neurons have considerably higher levels of non-CpG methylation than glial cells..The human male ES [embryonic stem] cell line (H1) is more highly methylated than the female ES cell line (H9).

Among the different types of non-CpG methylation (CpA [adenosine], CpT [thymine], and CpC), methylation is most common at CpA sites. For instance, in human iPS [induced pluripotent stem] cells, 5mCs are found in approximately 68.31%, 7.81%, 1.99%, and 1.05% of CpG, CpA, CpT, and CpC sites, respectively.”


The reviewers’ referenced statement:

“CpG methylation occurs during early development and does not increase over time.”

was presented outside of its context. The 2013 cited study’s statement was restricted to selected areas of the rodent hippocampus:

“Consistent with a recent study of the cortex, time-course analyses revealed that CpH [non-CpG] methylation at the selected loci was established during postnatal development of the hippocampus and was then present throughout life, whereas CpG methylation was established during early development. Maturing mouse hippocampal neurons in vitro also showed a gradual increase in CpH, but not CpG, methylation over time.”

Epigenetic study methodologies improved in 2017 had more information on CpA methylation.

http://www.mdpi.com/2073-4425/8/6/148/htm “CpG and Non-CpG Methylation in Epigenetic Gene Regulation and Brain Function”

Can researchers make a difference in their fields?

The purpose and finding of this 2017 UK meta-analysis of human epigenetics and cognitive abilities was:

“A meta-analysis of the relationship between blood-based DNA methylation and cognitive function.

We identified [two] methylation sites that are linked to an aspect of executive function and global cognitive ability. The latter finding relied on a relatively crude cognitive test..which is commonly used to identify individuals at risk of dementia.

One of the two CpG sites identified was under modest genetic control..there are relatively modest methylation signatures for cognitive function.”

The review’s stated limitations included:

“It is, of course, possible that a reliable blood-based epigenetic marker of cognitive function may be several degrees of separation away from the biological processes that drive cognitive skills.

There are additional limitations of this study:

  • A varying number of participants with cognitive data available for each test;
  • Heterogeneity in relation to the ethnicity and geographical location of the participants across cohorts; and
  • Relating a blood-based methylation signature to a brain-based outcome.

A 6-year window [between ages 70 and 76] is possibly too narrow to observe substantial changes in the CpG levels.”

All of these limitations were known before the meta-analysis was planned and performed. Other “possible” limitations already known by the 47 coauthors include those from Genetic statistics don’t necessarily predict the effects of an individual’s genes.

The paper referenced studies to justify the efforts, such as one (cited twice) coauthored by the lead author of A problematic study of DNA methylation in frontal cortex development and schizophrenia:

“Epigenome-wide studies of other brain-related outcomes, such as schizophrenia, have identified putative blood-based methylation signatures.”


Was this weak-sauce meta-analysis done just to plump up 47 CVs? Why can’t researchers investigate conditions that could make a difference in their fields?

Was this meta-analysis done mainly because the funding was available? I’ve heard that the primary reason there are papers like the doubly-cited one above is that the US NIMH funds few other types of research outside of their biomarker dogma.

The opportunity costs of this genre of research are staggering. Were there no more productive topics that these 47 scientists could have investigated?

Here are a few more-promising research areas where epigenetic effects can be observed in human behavior and physiology:

I hope that the researchers value their professions enough to make a difference with these or other areas of their expertise. And that sponsors won’t thwart researchers’ desires for difference-making science by putting them into endless funding queues.

https://www.nature.com/articles/s41380-017-0008-y “Meta-analysis of epigenome-wide association studies of cognitive abilities”

Science and technology hijacked by woo

I’m an avid reader of science articles, abstracts, studies, and reviews. I tried a free subscription to Singularity Hub for a few weeks last month because it seemed to be a suitable source of articles on both science and technology.

I unsubscribed after being disappointed by aspects of science and technology hijacked almost on a daily basis into the realm of woo. Discovering scientific truths and realizing technologies is inspiring enough to stand on its own. It’s sufficiently interesting to publish well-written articles on the process and results.

I was dismayed that the website didn’t host a feedback mechanism for the authors’ articles. We shield ourselves from information incongruent with our beliefs. It’s a problem when a publisher of science and technology articles similarly disallows non-confirming evidence as a matter of policy.

An article may or may not advance knowledge of the subject, and Singularity Hub enables author hubris in presenting their views as the final word on the subject. Directing readers elsewhere for discussion is self-defeating in that every publisher’s goals include keeping visitors on their website as long as possible.

Here’s my feedback on two articles that inappropriately bent reality.


Regarding What Is It That Makes Humans Unique?:

“This trait [symbolic abstract thinking] not only gives us the ability to communicate symbolically, it also allows us to think symbolically, by allowing us to represent all kinds of symbols (including physical and social relationships) in our minds, independent of their presence in the physical world. As a result, internal associations of novel kinds become possible.”

Why limit discussion of our capability for symbolic representations? Other features to explore are:

  • What is a belief if not a symbolic representation?
  • What attributes of human behavior provide evidence for hopes and beliefs as symbolic representations?
  • What is the evolved functional significance that benefits humans of using symbolic abstract thinking to develop hopes and beliefs?

“Our revolutionary traits stand out even more when we take a cosmic perspective..We are not only in the universe, but the universe is also within us..Our brains, as an extension of the universe, are now being used to understand themselves.”

This article should be written well enough to inspire without resorting to unevidenced assertions about revolutions, the cosmos, and the timing of brain functionality.

“Some of us possess higher consciousness than others. The question that we now have to ask ourselves is, how do we cultivate higher consciousness, structural building, and symbolic abstract thinking among the masses?”

What is the purpose of steering an evolution topic into elitism?


How a Machine That Can Make Anything Would Change Everything received >53,000 views compared with <5,000 views of the above article. This was an indicator that readers of Singularity Hub are relatively more interested in the possible implications of future technology than those of our past biological evolution. Why?

“If nanofabricators are ever built, the systems and structure of the world as we know them were built to solve a problem that will no longer exist.”

Soon we will have the worldwide solution to limits in food supply, energy supply, medicine availability, income, knowledge – all of the elements needed for survival?

I was reminded of the chip-in-the-brain article referenced in Differing approaches to a life wasted on beliefs. Each of us needs to address the impacts of past threats to our survival that include producing our present hopes if we are ever going to individually break out of these self-reinforcing, life-wasting loops.

“Human history will be forever divided in two. We may well be living in the Dark Age before this great dawn. Or it may never happen. But James Burke, just as he did over forty years ago, has faith.”

Is it inspiring that the person mentioned has had a forty-year career of selling beliefs in technology?

Yes, future technologies have promise. Authors can write articles that provide developments without soiling the promise with woo.

The pain societies instill into children

The human subjects of this 2017 Swiss study had previously been intentionally traumatized by Swiss society:

“Swiss former indentured child laborers (Verdingkinder) were removed as children from their families by the authorities due to different reasons (poverty, being born out of wedlock) and were placed to live and work on farms. This was a practice applied until the 1950s and many of the Verdingkinder were subjected to childhood trauma and neglect during the indentured labor.

DNA methylation modifications indicated experiment-wide significant associations with the following complex posttraumatic symptom domains: dissociation, tension reduction behavior and dysfunctional sexual behavior.”


Imagine being taken away from your family during early childhood for no other reason than your parents weren’t married.

Imagine just a few of the painful feelings such a child had to deal with then and ever since. I’m unloved. Alone. No one can help me.

Imagine some of the ways a child had to adapt during their formative years because of this undeserved punishment. How fulfilling it would be to believe that they were loved, even by someone they couldn’t see, touch, or hear. How fulfilling it would be to get attention from someone, anyone. How a child became conditioned to do things by themself without asking for help.

The study described a minute set of measurements of the subjects’ traumatic experiences and their consequential symptoms. The researchers tried to group this tiny sample of the subjects’ symptoms into a new invented category.

https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-017-3082-y “A pilot investigation on DNA methylation modifications associated with complex posttraumatic symptoms in elderly traumatized in childhood”


Another example was provided in Is IQ an adequate measure of the quality of a young man’s life?:

“During this time period [between 1955 and 1990], because private adoptions were prohibited by Swedish law, children were taken into institutional care by the municipalities shortly after birth and adopted at a median age of 6 mo, with very few children adopted after 12 mo of age.”

Swedish society deemed local institutional care the initial destination for disenfranchised infants, regardless of whether suitable families were willing and able to adopt the infants. What happened to infants who weren’t adopted by age 1?

Did Swedish society really need any further research to know that an adoptive family’s care would be better for a child than living in an institution?


A third example of the pain instilled into children by societies was related to me last year by two sisters. During the Chinese Cultural Revolution, 1966-1976, among other things, parents were required to be out of their households from dawn to late night, leaving the children to fend for themselves.

One of the daily chores for the sisters at ages 6 and 7, after attending school, was to buy food for dinner and the next day’s breakfast and lunch with ration coupons, and prepare the family’s evening meal. They never knew their four grandparents, who had died in ways the sisters either didn’t know or weren’t willing to express to me.

It wasn’t difficult to infer that traumatic childhood events still impacted the women’s lives 50 years later. My empathetic understanding of their histories, though, didn’t improve their current situations. I’ll highlight one of their many affected areas – accepting other people’s assistance.

One of the younger sister’s adaptations at ages 6 to 16 was – and still is – that she feels compelled to do everything herself. Her initial reaction is to reject help, no matter the circumstances. Her thoughts, feelings, and behavior impacted by childhood trauma have also included the opposite reaction of forcing family members – at their prolonged inconvenience and discomfort – to help others.

The older sister, on the other hand, accepts other people’s assistance, maybe too readily. She also lives alone, and sometimes has trouble providing for herself without excessive prompting from her sister. Her societal experiences apparently either taught her or reinforced helplessness.


It’s a challenge for each of us to recognize when our thoughts, feelings, and behavior are evidence of our own continuing responses to childhood pain that’s still with us, influencing our biology.

Let’s not develop hopes and beliefs that the societies we live in will resolve any adverse effects of childhood trauma its members caused. Other people may guide us, but each of us has to individually get our life back.

Europe, Asia, Africa, Australia, North and South America: every society has its horror stories, and there are people still living who can document last century’s events and circumstances. What evidence can be presented to show that traumatic effects on children from societal policies have ceased?

Epigenetic study methodologies improved in 2017

Let’s start out 2018 paying more attention to advancements in science that provide sound empirical data and methodology. Let’s ignore and de-emphasize studies and reviews that aren’t much more than beliefs couched in models and memes, whatever their presumed authority.

Let sponsors direct researchers to focus on ultimate causes of diseases. Let’s put research of treatments affecting causes ahead of those that only address symptoms.

Here are two areas of epigenetic research that improved in 2017.


Improved methodologies enabled DNA methylation studies of adenine, one of the four bases of DNA, to advance, such as this 2017 Wisconsin/Minnesota study N6-methyladenine is an epigenetic marker of mammalian early life stress:

“6 mA is present in the mammalian brain, is altered within the Htr2a gene promoter by early life stress and biological sex, and increased 6 mA is associated with gene repression. These data suggest that methylation of adenosine within mammalian DNA may be used as an additional epigenetic biomarker for investigating the development of stress-induced neuropathology.”

Most DNA methylation research is performed on the cytosine and guanine bases.


Other examples of improved methodologies were discussed in this 2017 Japanese study Genome-wide identification of inter-individually variable DNA methylation sites improves the efficacy of epigenetic association studies:

“A strategy focusing on CpG sites with high DNA methylation level variability may attain an improved efficacy..estimated to be 3.7-fold higher than that of the most frequently used strategy.

With ~90% coverage of human CpGs, whole-genome bisulfite sequencing (WGBS) provides the highest coverage among the currently available DNAm [DNA methylation] profiling technologies. However, because of its high cost, it is presently infeasible to apply WGBS to large-scale EWASs [epigenome-wide association studies], which require DNAm profiling of hundreds or thousands of subjects. Therefore, microarrays and targeted bisulfite sequencing are currently practicable for large-scale EWASs and thus, effective strategies to select target regions are essentially needed to improve the efficacy of epigenetic association studies.

DNAm levels measured with microarrays are invariable for most CpG sites in the study populations. As invariable DNAm signatures cannot be associated with exposures, intermediate phenotypes, or diseases, current designs of probe sets are inefficient for blood-based EWASs.”

How to cure the ultimate causes of migraines?

Most of the spam I get on this blog comes in as ersatz comments on The hypothalamus couples with the brainstem to cause migraines. I don’t know what it is about the post that attracts internet bots.

The unwanted attention is too bad because the post represents a good personal illustration of “changes in the neural response to painful stimuli.” Last year I experienced three three-day migraines in one month as did the study’s subject. This led to me cycling through a half-dozen medications in an effort to address the migraine causes.

None of the medications proved to be effective at treating the causes. I found one that interrupted the progress of migraines – sumatriptan, a serotonin receptor agonist. I’ve used it when symptoms start, and the medication has kept me from having a full-blown migraine episode in the past year.

1. It may be argued that migraine headache tendencies are genetically inherited. Supporting personal evidence is that both my mother and younger sister have migraine problems. My father, older sister, and younger brother didn’t have migraine problems. Familial genetic inheritance usually isn’t the whole story of diseases, though.

2. Migraine headaches may be an example of diseases that are results of how humans have evolved. From Genetic imprinting, sleep, and parent-offspring conflict:

“..evolutionary theory predicts: that which evolves is not necessarily that which is healthy.

Why should pregnancy not be more efficient and more robust than other physiological systems, rather than less? Crucial checks, balances and feedback controls are lacking in the shared physiology of the maternal–fetal unit.

Both migraine causes and effects may be traced back to natural lacks of feedback loops. These lacks demonstrate that such physiological feedback wasn’t evolutionarily necessary in order for humans to survive and reproduce.

3. Examples of other processes occurring during prenatal development that also lack feedback loops, and their subsequent diseases, are:

A. Hypoxic conditions per Lack of oxygen’s epigenetic effects are causes of the fetus later developing:

  • “age-related macular degeneration
  • cancer progression
  • chronic kidney disease
  • cardiomyopathies
  • adipose tissue fibrosis
  • inflammation
  • detrimental effects which are linked to epigenetic changes.”

B. Stressing pregnant dams per Treating prenatal stress-related disorders with an oxytocin receptor agonist caused fetuses to develop a:

  • “defect in glutamate release,
  • anxiety- and depressive-like behavior,

and abnormalities:

  • in social behavior,
  • in the HPA response to stress, and
  • in the expression of stress-related genes in the hippocampus and amygdala.”

1. What would be a treatment that could cure genetic causes for migraines?

I don’t know of any gene therapies.

2. What treatments could cure migraines caused by an evolved lack of feedback mechanisms?

We humans are who we have become, unless and until we can change original causes. Can we deal with “changes in the neural response to painful stimuli” without developing hopes for therapies or technologies per Differing approaches to a life wasted on beliefs?

3. What treatments could cure prenatal epigenetic causes for migraines?

The only effective solution I know of that’s been studied in humans is to prevent adverse conditions like hypoxia from taking place during pregnancy. The critical periods of our physical development are over once we’re adults, and we can’t unbake a cake.

Maybe science will offer other possibilities. Maybe it will be necessary for scientists to do more than their funding sponsors expect?