Thursday, November 7, 2013

The Violinist's Thumb by Sam Kean

Source of Book: Borrowed from the library

I previously read and reviewed The Disappearing Spoon by the same author. Sam Kean writes for the New York Times Magazine and Mental Floss, and has appeared on NPR. His books could loosely be called pop science: understandable to the average educated reader, without an abundance of footnotes and citations, but with significant intellectual content. Obviously, a professional scientist would consider them simplistic, and utterly lacking in the higher math they work with every day. Like Malcolm Gladwell - who I also enjoy - he tells a good story. Unlike Gladwell, who writes pop sociology, Kean has no need to make a point or suggest a solution to anything. Rather, his goal is to make an arcane area of knowledge enjoyable.

In his previous book, Kean discussed the elements and the periodic table. Eighteenth and Nineteenth Century science, essentially. For this book, he delves into what is a decidedly Twentieth and Twenty-first Century topic - that of genetics and DNA. 

The title, by the way, comes from the story of Paganini, who had unnaturally flexible fingers. The pieces he wrote 200 years ago - unlike most of the music from that era - still challenges the technique of the world’s finest violinists to this day. Playing Paganini is the sort of thing one does as an exclusive pursuit. The genetic source of Paganini’s physical advantages probably came from a defective mutation that caused him to become nearly crippled at a relatively young age, which is why his story makes it into the book.

What I have found is that while most people tend to acknowledge the truth of atomic theory - even while failing to understand or spectacularly misunderstanding it - they don’t tend to have heated opinions about chemical reactions. Genetics is a whole other beast. Most people lack even a basic knowledge of what DNA is and how it works. But that certainly does not stop them from having violently strong opinions about genetic issues. And many deny even the best understood and proven scientific facts about genetics. I’ll make specific mention here of the O. J. Simpson trial, which took place during my first year in law school. Much of the prosecution’s case turned on DNA evidence, which failed to impress the jury, who preferred doggerel poetry as the best explanation. (“If it doesn’t fit, you must acquit.”) Although my own theory is that Mark Fuhrman’s use of racial slurs would have sunk the case in any event. Another contemporary issue was the drive to require warning labels on genetically modified food here in California. In that case, there was a lot of heated rhetoric centering on what is “natural” (such as human directed hybridizing and mutating using toxins and radiation) and what is “unnatural” (directly manipulating the DNA). Instructive in this debate might be C. S. Lewis’ excellent discussion of the word “nature” in Studies in Words, which I reviewed here. (“Natural” often meaning “what I like.”)

For those who get the heeby-jeebies about intentional manipulation of genes, I recommend you avoid this book. On that level, it is highly disconcerting because recent discoveries have upended some of what we popularly believe about the nature of humanity and our conception of nature as static and clean and perfect.

Let me just lead off with the one that blew my mind the most. Viruses (which occupy the weird line between living and non-living) are notorious for rapid mutation and evolution. This is why the flu shot has to be different each year. All the related flu viruses combine and swap genetic information whenever they are present in the same host. Plus, random errors in DNA and RNA transcription occur, and stuff gets moved around and lost, and imported from the host creature, and all kinds of crazy stuff. Viruses are essentially a bad carbon copy system that makes billions of copies really fast.

Here is where it got freaky: not only do viruses steal our genes, they insert their own into our DNA. Not every time we get sick - our error-check system is better than that in viruses. And what mutations we do get from viruses typically only affect the infected cells, not our reproductive cells (egg or sperm). But once in a while, they do. And, since viruses reproduce like crazy, the insertions add up. Viral genes can be recognized by a combination of two ways. First, some genes are easily seen to be virus genes because of the proteins they make (to form the viral shell). Second, if certain stretches of DNA in the human genome show the same unusual (for humans) genes, but placed in different places in a seemingly random order, the chances are, it is junk. Stuff placed there by an error. So, apparently, we have a lot of virus DNA accidentally spliced into our own.

Yeah, this sounded like it might be a stretch. Until a guy named Thierry Heidmann went through and re-created a virus from this material. Yes, he actually located and spliced together the pieces. It looked similar - but not exactly like - known modern viruses.

Now, freak out time. He injected the reconstituted virus DNA into living cells from various mammals. And they caught the disease. (A very mild, rather benign infection, fortunately.) The virus replicated itself and infected new cells.

Now remember, viruses are quasi-living. They reproduce, but they require a living cell to do so. They cannot process food or create waste or reproduce without the use of a living cell. Thus, they may or may not be “alive” as we consider it. But still, an “extinct” virus was resurrected purely from the DNA found interspliced in ordinary human DNA.

(Yes, this is the premise of Jurassic Park, originally written by the fascinating Michael Crichton. It would/will be much, much harder to re-create a more complex extinct organism because viruses are merely DNA or RNA in a protein capsule. Insert the genetic information into the cell, and the cell assembles the parts. A lizard would require a very similar lizard to develop the egg and sperm and develop the grown creature. It may well turn out to be impossible. Or at least unlikely.)

I’ll mention a few other interesting things. Just like in the case of the so-called Big Bang (which I discussed in Why Does the World Exist), originally, the discovery of DNA was considered a threat to Darwinism. If all traits of all living things were determined by an inviolable code, then they cannot have changed over time. Later, of course, it was discovered that DNA does in fact mutate - and much more often than originally thought. Obviously, there are many unanswered questions. The specifics of development from simple to complex defies an easy explanation, but a genetic explanation of inherited traits doesn’t preclude one or the other.

One of the most interesting parts of this book was the history of the fruit fly experiments, which formed the basis of much of what we know about genetics. Just a fascinating story.

Also intriguing was the long term experiment in genetic mutation that arose in the case of Hiroshima. Nothing like bombarding a large population with strong radiation, and then checking to see what happens over the next 70 years. I found it interesting that, despite the potential for great damage, the rates of cancer for the survivors was surprisingly low. In particular, those unlucky individuals who managed to get hit by both bombs were far less affected than expected. For the most part, they went on to live normal lifespans and die of normally expected diseases. (Yes, plenty died of cancer - often in their 90s, though. Which may well have occurred anyway at that age if they missed out on heart disease.) Human and animal bodies are remarkably resilient, particularly to short term exposure. What doesn’t kill us may not always make us stronger, but it doesn’t always weaken us either.

Another great fact was the application of knot theory to DNA. In a development that will come as absolutely NO surprise to any musician who uses cables, if you put a rope in a box and jostle it for a while, it will form surprisingly complex knots by itself. DNA is similar. It makes knots that must be untangled for copying. In fact, in light of all the things that can easily go wrong, it is amazing that we can reproduce at all.

I’ll also note the interesting - and unsurprising - fact that many of the great developments in genetics that came from the work of women came from the work of nuns. Why? Well, a woman in the not very distant past was expected to give up her career on marriage. A woman who remained single was looked on with suspicion, and rarely if ever could make her living at science. So who might be able to devote the time to scientific pursuits without being pressured to marry or ostracised if they did not? Well, why not those who had devoted their single lives to the service of God?

(Side note: if my wife had been born 100 years ago, I believe she would have gone this direction. As it was, she was sure she would never marry, because she had ambitions beyond the kitchen, which was unacceptable in the group she grew up in.)

Finally, I give bonus points to this book for addressing the ethical issues in genetics in a dispassionate and informative manner. One of the big ones has been the issue of genetics and race. Even Watson (of Watson and Crick - discoverers of the structure of DNA) tried to make a political statement about the “error” of failing to acknowledge the inferiority of certain races. (Guess which race was singled out as inferior?) And yet, despite fanfare, the supposed “smart gene” which certain races have less of, turned out to not, um, determine intelligence after all. But it sure tends to make news! In this context, the problem of nature versus nurture arises again and again. Both are tied up and possibly inseparable. And while genes for specific diseases have been found, the big traits such as intelligence and strength appear to be determined by many genes and possibly other genetic markers yet to be discovered.

Kean also notes the controversies over genetic manipulation. If we could some day cure cystic fibrosis (to give one example) by repairing the broken gene, that would be an unmitigated blessing to mankind. However, the means of manipulation are often misunderstood, and attacked as “not natural.” (Reminder, disease is very natural.) However, other manipulations are fraught with ethical issues. Cloning gets a specific mention, for the risk of making clones, not to be viewed as separate humans, but as organ harvests, for example. That said, I appreciate that Kean notes that clones have been living among us since the dawn of life. We call them identical twins, but genetically, they are simply clones: identical at the genetic level. But clearly separate persons - and different despite the identical DNA.

As with Kean’s last book, I found it to be a good read. However, prepare to have some of what you thought you knew challenged. It is difficult to look at life the same way after reading this book.

Note on the Human Genome Project:

One of the juicy stories in this book was the contentious race between the National Institute of Health and the private company Celera to completely sequence the human genome. (Essentially a road map to human DNA.) I won’t attempt to recount the whole thing, but it was like the Ben Hur Chariot Race of science nerds, with plenty of trash talk, some dirty deeds, and a whole lot of finger pointing and chest pounding afterward. In fact, the controversy continues today, with NIH still trying to get sole credit for the discovery.

Here is a recent article, if you are interested in reading more.

This wasn’t helped at all by the fact that J. Craig Venter started out with NIH, and then grew impatient with the pace, started Celera, and then invented techniques which vastly improved the speed of sequencing. (Thereby pushing NIH to improve their process.) Venter was, shall we say, a “difficult” person. Brilliant, but difficult.

In fact, most who worked with or against him preferred a more “colorful metaphor,” as Spock would say.

(No, I cannot possibly resist using that reference and posting a clip. I love this movie. Also, I’ll note that my dad’s favorite line was “Ah. The giants.” 

Note on Paganini:

Do you really think I could write about Paganini without adding a clip?

Paganini’s Caprices are legendary among violinists in the same way that Bach’s Sonatas and Partitas are. Amazing invention combined with profoundly and maddeningly impossible technical demands. (In Bach’s case, the use of a solo instrument to play three and four part fugues, for example.)

Carprice #24 is famous because its theme was borrowed by several composers as the basis for their own sets of variations. The best known is Rachmaninov’s Variations on a Theme of Paganini, for piano and orchestra, which is one of my favorite piano works.

Here is Hilary Hahn, showing her chops. I will particularly note the left hand pizzicato section beginning at the 2:58 mark. Holy moley! I wish I could play like that…

For those who care, the second piece is Nathan Milstein’s Paganiniana, his own set of variations on Paganini’s theme.

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