Tuesday, September 01, 2020

Getting acquainted with yourself

 kw: book reviews, nonfiction, science, genetics, epigenetics, microbiome

Just over 17 years ago the Human Genome Projects were completed. There had been much hype about the wonderful things that we would learn and be able to do. And hype it was. The more we've learned, it seems the less we know. During the near-decade that the projects ran I noticed, in science fiction in particular, quite a bump in stories about genetic enhancements of all sorts, from cloning to adding all manner of "features" to people; one story was about "getting genes twanked," as though one could go to a "gene mechanic" and have parts swapped in and out as desired.

Reality isn't that simple. The Genome is one thing. It took years just to figure out how much of our DNA is really a part of our genome. A depressive low occurred in many of our minds in 2003, when we learned that we have "only" about 22,000 "protein-coding regions", the new term for what we used to mean by "gene". In what follows I'll call them CR's. I have recently read that there are about an equal number of "non-coding active regions". I'll call them NR's. It seems they mostly make RNA that doesn't get turned into protein, but has its own functions. Some NR's are regulatory, in that they make a bit of RNA that regulates a CR. Nobody seems to know what the others do. 

Apparently, the original set of CR's comprised about 2% of our DNA, or about 60 million base pairs of the 3 billion total. The NR's may be smaller, but not by much, so that the total DNA that is "active" (so far as we know) is more like 4%, or 100-120 million base pairs. Together, CR's and NR's are now called "exons", because they get expressed in one way or another.

About twice as much DNA, some 8% of the "human" total, consists of virus genomes, stored essentially intact, though mutated over time. Most of this is from retroviruses, calling cards left by virus diseases of prior generations. Some of the fresher ones can apparently still be reactivated on occasion.

The regulatory NR's just begin to scratch the surface of the ways DNA expression is modified. They are mainly responsible for the differences between the hundreds of different tissues in our bodies, each of which requires a unique set of DNA expression profiles.

The word "epigenetics" was apparently coined in the 1880's. It was at that time kind of a side issue to natural selection, and smacked of Lamarckism (inheritance of acquired characteristics). At present there are at least two known chemical methods by which environmental events influence DNA expression. They don't change the DNA code, but attach things like methyl groups to the DNA backbone to silence an exon, for example.

Some of these can be passed on to future generations, so there is indeed a bit of Lamarck in our Darwin cocktail! I went looking for books that described more about epigenetics, and found Pleased to Meet Me: Genes, Germs, and the Curious Forces That Make Us Who We Are, by Bill Sullivan. The book is about a lot more than epigenetics. As the subtitle indicates, our resident microbiome also affects what we do, what we think, and who we are.

Just to complicate the picture, while we're pretty sure the 8% of our DNA that used to be viruses isn't doing anything, if we subtract out that and the 4% that we know to be active (the exons), a full 88% of our DNA has no known function. Nature is parsimonious; why keep it all? It is costly to produce and maintain, so what is it for? Boy, do we have a lot to learn! It may just be that, under the hypothesis of "selfish DNA", lots of "other" DNA is carried along in all eukaryone genomes, just because it can. There is certain to be more to it than that. We just don't know yet.

What else is going on? Somehow our collection of exons is able to be expressed into more than a million proteins. The Proteome is vastly more complex than the Genome! Then there's the Saccharome, the collections of sugars and sugar "cousins" (including the ribose and deoxyribose that form the backbone of RNA and DNA respectively) and sugar polymers, which just might number in the tens of millions! There might be other "-omes" out there, but I haven't read about any.

If you were to put a human body (suitably deceased, of course) into a big blender, then extract all the DNA, you'd find a lot more than the human set of exons and the rest of the human genome. You'd find millions or billions of other exons in the mix. If you could take a census of all the cells that made up that same body (before the blending!), you would find 20-30 trillion human cells. You would also find between 100 and 200 trillion microbes of an unknown number of species, mostly residing in the gut. Together, they weigh about as much as the brain.

After a chapter ("Meet your Maker", which is DNA) about DNA and its history in science, we find nine chapters that mainly discuss aspects of our personality. After all, irrespective of the kind of body we have, who we ARE is mainly a matter of what we DO, which depends on what we THINK and FEEL.

The chapter on Taste begins with differences between our tongues. "Supertasters" are more sensitive to many tastes (and "supersmellers" are also, to but different aspects of the "taste" of our food). But it isn't just about whether broccoli tastes bitter or DMSO tastes sweet, or the subtle (or not) aroma of port wine. "Taste" has a social element, and a great many things not food-related are said to be in "good taste" or "bad taste". In each chapter, although much attention is given to different bits of DNA that make us different, we find, for example, that the things our mothers enjoyed when we were in utero affect what we like or dislike later on. How can this be? Epigenetics. Furthermore, the kinds of foods your parents like affected their microbiomes, and this in turn set you up, during and after birth, to have certain species in your own microbiome…and the bacteria inside you have their own likes and dislikes!

I'm finding it hard to pin down the point of this book. I suppose I could express it this way: our DNA isn't everything. The "hand" we are "dealt" by nature has a certain range of potential, but epigenetics and microbiome dynamics narrow the possibilities. So does our environment, whatever "slings and arrows of outrageous fortune" we might have endured. The life we live makes epigenetic marks on our genome, and, even if we never take antibiotics (rare!), can dramatically modify our microbiome. The inner residents, in turn, affect what we like, how we think, and perhaps even how we vote.

In the chapter "Meet your Beliefs" we learn of studies of children's personalities, and how this affected their political stance two decades later. Reporting on work by James Fowler of UC San Diego: "Progressive liberals more commonly possess the daredevil variant of DRD4 (a gene that affects the brain) than conservatives." (p 248) And quoting Jack and Jeanne Block of UC Berkeley, about a study of youngsters in nursery school and then two decades later:

"The relatively liberal young men, when in nursery school two decades earlier, … [were viewed as] resourceful and initializing, autonomous, proud of their blossoming accomplishments, confident and self-involving. The relatively conservative young men … [were viewed as] visibly deviant, feeling unworthy and therefore ready to feel guilty, easily offended, anxious when confronted by uncertainties, distrustful of others, ruminative, and rigidifying when under stress." (p. 249)

There was a similar list regarding young women and their characteristics as children. The loaded language of the quotes shocked me. It made "liberal" youngsters seem angelic and "conservative" ones seem deplorable. This is no surprise to me: I know Berkeley. I spent time there around the time these studies were carried out (not knowing that at the time, though). It is a source of the leftist ideology that loudly demands "first amendment rights", but only for people who think like them, and denies any rights to all others. A friend of mine, who calls National Public Radio "Radio Managua", calls Berkeley "Little Moscow". What we really see in the work of the professors Block is the effects on children who either agreed with their nursery school teachers, or who didn't. During the time of these studies, the formative years of today's radical leftists, you couldn't find a conservative teacher in any public school in Berkeley to save your life.

So let's look at the second set of adjectives through another lens, one that removes the pejoratives:

  • deviant → self-starter or thinks independently
  • feels unworthy → doesn't jump to conclusions or is open to other ideas
  • feels guilty → unafraid to accept responsibility
  • easily offended → strong sense of right and wrong and not afraid to say so
  • anxious → resists being forced into false dichotomies
  • distrustful of others → distrustful of teachers who punish independent thinking
  • ruminative → this is the only positive in the list! Leftists tend to be self-blind.
  • rigidifying under stress → unwilling to be cowed by bullying

I wonder how the study, performed about the time Dr. Sullivan was in short pants, would have described children if it were begun at Kansas U in the 1990's and the children revisited about 2010?

A significant part of the same chapter, and much of the last chapter, are a bit of Atheist Evangelism. Dr. Sullivan and other evangelical atheists would do well to read Evidence That Demands a Verdict by Josh McDowell. I didn't "think" my way into being a Christian. I had transformative experiences, and continue to experience them. Perhaps Dr. S. would call me mentally unhinged. So be it.

Regardless of such defects (and others; I could have dwelt on his frequent, flat attempts to inject topical humor that would only appeal to Millennials), there is much useful information in this book about what makes us US. But I'll keep looking to find a volume with equivalent or greater breadth that I'd be able to recommend without reservation.

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