Tuesday, April 30, 2013
"THE EPIGENETICS REVOLUTION" by Nessa Carey
Epigenetics are barely recognized as a new field, greatly expanding the number of questions we have about human bodies and how they work. The research is tentative, complex, hard to assimilate. The human genome becomes easier to “read” daily, but it is a only the basic manuscript. Epigenetics are the annotations, the blue pencil remarks that indicate both additions and deletions: they can make all the difference.
One kind of annotations is the histones that are like the spindle or spine that the genes are wrapped around to make their helix, a kind of spiral, and they can make that helix -- sort of like the wire binding on a notebook -- tighter or looser, which can make the genes able to get their message out more easily or with more difficulty, as though the tighter the binding, the harder to turn the pages.
Another kind is methylization, a little molecule that says NOT. It turns genes off. (I’m now running into this term everywhere.) It doesn’t remove a gene -- just shuts it down. But then there’s another little molecule that adds to the methyl molecule and that says “TIS, TOO!” and turns it back on.
When the two-sided zipper that creates a new person by unzipping, then rezipping with someone else’s opposite zipper side, the father’s side loses all the methyl attachments -- all the notes are removed. But some are guarded somehow. And the mother’s notes are now applied to the father’s zip, with new results.
Environmental circumstances can write new methyl notes or wind the histones tighter or looser, and these can persist up to three generations or beyond. It appears that my weight struggles may be related to my grandfather’s poor nutrition in Scotland at the turn of the 19th century. This particular sequence affects females rather than males, for some reason. The genes of each half of the zipper are marked with little tags that say whether they came from the sperm or the ovum, and they interact as well, so they can footnote methylization.
Over a decade or so, ten per cent of a person’s epigenetics may change as they grow, move to a new environment, change practices. There are drugs and strategies that will turn these epigenetics off and on, add and subtract, but the genes themselves are hard to alter. In fact, one of the functions of the epigenetics is to guard the genes and repair them if they get broken. It is the patterns that count more than the individual genes -- if 3, 5, 8, and 14 are off, the results will be different from 3, 5, 6, and 24 being off.
Early childhood abuse can alter at least two molecular pathways that create epigenes, one through the adrenals excreting cortisol -- I suspect also through direct damage to the adrenals since a favorite kind of abuse is a beating on the back right over the adrenals, which are on/above the kidneys -- and the other through the hippocampus which is the result of existing in a hostile social environment. The research for this is done on a little mouse that is put into a cage with a big mean ugly hostile mouse. Like a bad step-dad. Or an abusive school situation where bullying is tolerated. No doubt sexual abuse has its own pathways, but they are not in the book I’m reading.
This book is by Nessa Carey, an English scientist. The title is “The Epigenetics Revolution” with the sub-title of “How Modern Biology is Rewriting Our Understanding of Genetics, Disease and Inheritance.” There are many little side trails, one of which is about cancer. Cancer drugs and HIV drugs have a good deal of overlap, and some of them work in similar ways -- adding or subtracting these small epigenetic elements. The epigenetic approach works better on cancers of the blood, possibly because the “annotations” can penetrate into the script of the liquid genome more easily than they can get into the solid masses of other kinds of cancer. Several kinds of epigene-triggered cancer affect T cells, which are part of the HIV puzzle. The idea is that epigenetics confuse the cancer protection systems (cancer is a phenomenon of the broken genome control of the cell but may be a complex system of this-turned-off and that-turned-on) and that every virus is code, just like the genome. In fact, there are several epigenetic phenomena either woven into the actual genome or showing up attached to it some way that are believed to have originated as viruses.
It’s almost scary that the parallel to computer code is so apt. Punctuation in the wrong place, a stutter, a copy-and-paste in the wrong place, and the person is crippled to some degree. The links don’t work anymore. There’s an “upstream/downstream” which means that there are triggers, just as there are in software. if you miss passing the trigger, the performance of the code changes.
These are quite apart from mutations, which means actual genes added, changed or subtracted, which are far more permanent changes than epigenetic tags. Red hair, blue eyes, and so on are gene mutations. No one knows whether it might be possible to turn the gene for alcoholism off or maybe even turn PART of it off, in case the rest of that gene (which can be very long and full of code) is some kind of genius we don’t want to lose. There is a notion of which gene it is that causes addiction to opiates, but no real plan for how to turn it off. The same for amphetamines.
A new generation that thinks about human behavior problems in code instead of the persisting parent generations that have hung onto behavior-modification through reward and punishment might change our whole society. We hope. But maybe it would be worse. What if genes could be methylated or not at will, maybe by plugging the whole genome into a computer system programmed to “heal” what is missing or what is overactive? Who would decide what to put in or take out? And then there is the constant problem presented by who gets access to such a treatment -- the rich, probably, and more likely in the developed world, which creates a moral problem. Often risky strategies for fighting disease are tried out on people who have arrived at their last resort, which makes results hard to interpret, or on people no one cares about, like prison inmates -- which is a whole different moral problem.
The book constantly brings up the difficulties presented by things like Big Pharma and the problem of how to get meds into people (pills, IV, implant, maybe technically across the brain barrier, or through steady dedication to protocol). We struggle on, “methylating” with alcohol or pot, rebooting with a nap or a long walk, maybe even reprogramming. But increasingly we realize how complex this is, how woven together we are, how much everything changes all the time. How much the culture “methylates” us. This account of mine is indubitably at least partly wrong and certainly only a start of my understanding. But this limitation is also true -- on quite a different scale -- in terms of the major scientists working on this stuff. This book was published at the beginning of 2013. It’s probably already out of date. But the vocabulary is useful.