Posts Tagged ‘DNA’

Gene Therapy

Monday, September 8th, 2008 by Terence Witt

I had a friend ask me the other day where he could get one of those green ‘glow-in-the-dark’ cats he had read about. He wanted one for his girlfriend’s birthday. “Can I get one that starts blinking when it’s hungry, and what other colors were available?” His sense of humor is almost as dry as mine, so I’m still not sure whether or not he was baiting me. Just in case, I told him that I thought that he should go to his nearest chain pet store to pre-order one, but I didn’t think the blinking version would be out until just before Christmas.

Then he wanted to know how soon it would be before the Army created genetically enhanced super-soldiers or chimps could be modified to drive cars. I told him that the Army would probably opt for ‘Killer Robots’ to avoid the ethical hassles associated with playing with the human genome. As to chimps driving cars – they already do (see Jared Diamond’s excellent book, The Third Chimpanzee for why humans are actually one of the three native species of chimps on Earth).

The best way to understand the challenges of genetic modification (aka gene therapy) is to embrace the complexity of our genome. The execution of good aroma therapy, for instance, requires the ability to put odd smelling stuff in wax and light a candle. Now I’m sure there’s a lot more to this than meets the eye, but it is simply not very difficult to get some sort of beneficial, soothing effect, with technology that was available thousands of years ago.

Compare gene therapy. Imagine that you’ve got this computer program, 3.2 billion code words long, and you really don’t know what most of it does. Now imagine that this program operates by exposing portions of its code to its environment, using what amounts to a protein mask. Some parts are running, others aren’t, based on the parts that are covered up by this mask. Different parts of this mask are permanently configured in different cells, such as the parts that are always exposed in a liver cell but concealed in a bone cell, and other parts of this mask open and close depending on enumerable environmental factors, such as ion concentrations and the presence or absence of thousands of different molecules. So bits and pieces of this mask are winking on and off all the time, in every cell in our body. And that’s just the main code. Beyond this code, there are all sorts of micro-codes scattered through a cell’s cytoplasm that tells the cell how its monstrously complex genetic code is to be interpreted. Also consider that our 3.2 billion code genome, if stretched out as a single molecule of DNA, would be about six feet long. Yet it is so thin and coiled so tightly that it fits inside of a cell’s tiny nucleus. If you don’t think this system is absolutely remarkable, then you just haven’t been paying attention.

So now you set up to program this code nightmare. You have some piece of code you want to run, say, to make your hair green or your skin transparent (creepy!). If this were a computer program, you would just find the appropriate place to add the subroutine, QED. But with the genome, you have two problems. First, you don’t really know where to put it because you don’t really know how the program works. The second problem is that you can’t really control exactly where it goes. This second issue is the truly bad news. Regardless of how the code is delivered (sometimes even shot into a nucleus), whether or not it will ‘take’ depends on where it actually combines with the genome, which is to a large extent random.

There are, after all, only four letters to our wonderful genetic alphabet, and only short sequences can be used to match some location in the genome. So if your matching code is, say, 6 letters long, then the number of places that it might match in the genome is 3.2 billion divided by 4 to the 6th power, or about 800,000 different locations. Now add the fact that the availability of many of these locations winks on and off depending on the environment. Yikes.

Yet even in spite of this staggering complexity, progress is definitely being made, and each new step overcomes monumental odds. But as it stands now, it would be easier to build a shopping mall on the moon than confront some of the technical challenges waiting inside each and every one of our tiny cells. So the next time you get down on yourself for missing a three foot putt or can’t remember where you left your car keys, just keep in mind that you’re running some of the most complex software imaginable. There’s bound to be a few bugs.

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