Genetic byways

kw: book reviews, nonfiction, genetics, essays

It is a rare book in which I learn something from every chapter, but such is The Violinist's Thumb: And Other Lost Tales of Love, War, and Genius as Written by Our Genetic Code, by Sam Kean. At first, I expected a kind of send-up of Stephen Jay Gould's The Panda's Thumb, but not so. Rather, the book is a delightful exploration of some lesser-known stories told with and by DNA, from the pen of a sprightly writer.

The title episode is not a chapter subject, but part of one: Chapter 12 explores the genetics of art, artistic expression and ability, with Niccolò Paganini as the centerpiece. Paganini's short career as a violinist was so remarkable the Catholic church refused to bury him on sanctified ground, suspecting he had a pact with the devil. His promiscuous private life and generally atheistic tendencies didn't help. He was actually inflicted with a genetic defect that left his connective tissues exceptionally loose, thus his fingers, and his left thumb in particular, could perform reaches on the violin's neck that were considered unhuman. While he became the greatest violin virtuoso ever known, he suffered continual illnesses, fragile skin, a shortened career, and an early death (well, not too early: age 58), what some called "payback" for his incredible talent.

Other talents with a genetic link include "perfect pitch", the ability to recognize a note and whether it is exactly in tune. Different sources state that this ability is found in between one and ten persons per 10,000, but is much more prevalent among those who have a close relative or two with perfect pitch. Good relative pitch is more common (perhaps 10% of us): This is the ability to properly tune an instrument such as a guitar or even a piano using a single perfect tone for reference. Until I bought an electronic tuner a few years ago, I tuned instruments using a tuning fork, the 440Hz "A". People with lesser skills can usually tune a guitar if they have a well-tuned one or a piano to compare with ("good relative pitch"). Electronic tuners make it much easier for folks with poorer pitch discrimination to tune a guitar or banjo or mandolin. My grandfather could tune a piano, including the proper "stretch" above and below the middle two octaves, by first tuning the A above Middle C to a 440Hz fork, and going from there.

But not everything is genetically determined. Kean explores epigenetics—which lends partial support to that anathema of natural selection, "inheritance of acquired traits"—and shows how certain life experiences can affect children and even grandchildren and further. Shades of Biblical curses "to the third and fourth generation".

He also reveals the real obstacle to human cloning. Primate ova have a more complex and delicate system of spindle structures that participate in cell division. Removing and replacing the nucleus from a sheep ovum to produce Dolly, and later successes with cats and several other species, depended on extracting the nucleus while leaving the spindle system intact. This is just barely possible (one success in 400 ova, in the case of Dolly) with more robust mammalian ova, but no technique has yet been even imagined that will work for human or ape, or probably even monkey, ova.

The biggest learning for me is that DNA doesn't unwind cleanly when being duplicated or expressed to mRNA. A cluster of enzymes snips one strand of the DNA, lets a bit of unwinding proceed, then re-welds it. This has to happen properly many times for the expression of a single gene, and an untold number of times during mitosis and meiosis, when DNA is totally unspooled and duplicated. I didn't learn whether this snip-weld sequence occurs only on the "copy" strand (the one not being expressed), but I suspect that is the case. I also wonder if it is the same in bacteria…

The big mystery resulting from the Human Genome Project, now a decade in the past, is why humans have so few genes, something like 24,000. It was confidently predicted in the 1990s that we must have 100,000 or more. Known protein-coding segments of our DNA make up only 2% of the 3 billion bases, about 60 million. At least 8% of our total DNA came from viruses, and possibly much, much more. But those and the rest of that 98%, far from being the "junk DNA" that some benighted scientists once sneered at, seem to include a very large "regulatome" (my coining), that not only determines when a "gene" is expressed, but which of several proteins to make from it via RNA editing. The central dogma of genetics—DNA to RNA to unique protein—is now long dead. A protein is now realized to resemble a sentence made from several words, rather than a single long word. Editing gathers a number of components, from one or more "genes", to produce the sentence. This is what turns 24,000 protein coding segments (we need a new term; "gene" is enormously inadequate!) into a few million proteins and peptides.

Genes are not destiny. This is similar to physiology; if you get an "exploratory" CT scan, the radiologist will probably point out between 5 and 15 anomalies. None of them is likely to cause trouble. Some imaging centers, with idle scanner time and a large mortgage to pay on it, advertize things like whole body scans. You know the proverb: look for trouble and you are sure to find some. Many people carry "the gene for" something, but never experience what that something is. And now that you can get your whole genome sequenced for one or two thousand dollars, should you? I say, don't look for trouble unless you have a real reason for doing so, such as three out of four grandparents who died in their 50s of heart attack. Even then, the DNA sequence won't tell you anything new. You still have to eat your veggies, get your weight down, and exercise and maybe you'll survive into your 60s. With different grandparents, perhaps you'd live to your 80s or 90s, but remember Jim Fixx? He was a member of Mensa and a long distance runner who died of a heart attack at age 52. Was that such a shame? Because without all that running and eating well, he'd have died much earlier, like most of his relatives. He did what he could with what he had. That's the most any of us can ask for.

Cause and effect are hard to untangle. People studied Einstein's brain to find if he had something special they could see. He did have an extra-large parietal lobe, which might have helped his genius. But was it inborn (we don't have his parents' brains to compare), or was it because he was an accomplished violinist? Did a big P-lobe make him a better violin player or better scientist, or did his violin playing make him a better cosmologist, P-lobe or no? He thought so. We don't know enough about both genetics and the nurturing of young geniuses to tell, even a little. It'll take decades of study to learn even a little, and perhaps we would be the poorer for it, rather than for the better.

A song chorus I wrote in 1996 says, "We are dealt the cards, but our own hand we play". This could be a theme for half the chapters in this book. What we think we know is still just a trifle compared to what there is to know.