f you're reading this, chances are you've just downloaded a file (several, actually) from Science Fiction Weekly's computer to your own. This familiar process is often aided by digitally compressing the file into a smaller package before it's sent. When this is done, another program has to be run at the receiving computer to examine each character (or "byte") of the compressed file, and either save it directly to memory or else unpack it into two or more bytes (based on header instructions buried in the preceding bytes). Sometimes, several passes over the data are required to restore the original large file in all its glory.
The complex proteins that make up your own body are encoded in your DNA using a similar scheme. Some proteins are purely structural, meant to hold your cells together in the proper shape, or to provide strength or rigidity. Others, known as enzymes, are chemical catalysts that keep your metabolism working smoothly. Still others are hormones, chemical messengers that tell different parts of your body how to behave, and finally there are receptors, molecules into which the hormones fit, like keys into biochemical locks. But all of these molecules are constructed in exactly the same way: by tiny machines called ribosomes, which string amino acid molecules together like beads, forming long, ropy necklaces based on the instructions in your cells' nuclei. A DNA sequence of, say, ACATTA codes for the amino acids
Serine (ACA) and Leucine (TTA), in that order, and equivalent
three-letter "codons" identify up to 18 other amino acids in
whatever order a particular protein requires.
Actually, it's a bit more complex than that, since a gene--a sequence of DNA that codes for a complete protein molecule--has "intron" (header and footer) sequences to separate it from other genes, and some genes are "promoters," which are capable of switching other genes on or off at pre-programmed times in a process known as expression. So the genome is not so much a sheet of music as an endless player piano reel that is constantly enabling and disabling its own notes and phrases. And the notes themselves are subject to modification by viruses, transcription errors during cell division and, more recently, by the deliberate if somewhat haphazard tinkering of biochemists.
Beefy, indulgent mice
The latest example of this hacking is a strain of obesity-resistant mice that can eat all the french fries they want without gaining unwanted ounces. Responsible for this tiny miracle is a gene called HMGIC, which codes for proteins that apparently help normal mice to store fat. When this gene was damaged (or "knocked out") by Dr. Kiran Chada of the University of Medicine and Dentistry of New Jersey, the mice lost this ability, and in fact develop only about 10% of the body fat of normal mice, regardless of diet.
This was not the first such weighty experiment. Other strains of knockout mice have lost related traits such as the hormone leptin, which is normally released by fat cells as a message to the brain to eat less. Like many hormones, leptin moonlights in other parts of the body, playing a not terribly well understood role in the immune system and in the growth of new capillaries, which is why the mice that lacked it were fat, sickly, and prone to overindulgence. Not all genetic engineering involves disabling genes, though; last year, researchers in Pennsylvania and London inserted extra copies of the muscle-enhancing IGF-1 (insulinlike growth factor) and MGF (mechano growth factor) genes into mice, along with a special "promoter region" to ensure the new genes were always expressed. The resulting mice were beefy indeed--20% more muscle mass than a standard mouse, with no additional exercise.
Each time a discovery like this is made, headlines tell us that the root cause of obesity has been found, but alas, the riddle is not so simple. Mouse studies have implicated many other genes in different aspects of body weight and composition, including UCP2 (uncoupling protein 2, which triggers the burning of fat to elevate body temperature), and POMC (which codes for a hormone called MSH, which regulates both appetite and fat storage). Only when the interplay between these (and probably other) genes is mapped will obesity be truly understood.
My favorite rodent experiment is a grisly demonstration of cross-species gene transplantation: hairless mice with non-functional but full-size human ears growing out of their backs. The idea here is to use mice as a platform to grow "real" ears for people who've lost their own and are making do with plastic replicas. Such "xenotransplantation" faces a number of ethical and immunological hurdles before it can actually be tried, however. Interestingly, genetically engineered traits are not limited to the physical. In La Jolla, California, scientists at the Salk Institute have deprived mice of the gene CRHR2, or corticotropin releasing hormone receptor 2. This knockout appears to make the mice "neurotic," i.e., more cautious, and with a much quicker and stronger stress response. Presumably, a host of other emotional traits can be engineered as well.
Über-rodents bent on global domination
Perhaps the most troubling bit of tampering came last year, when a Princeton University project endowed mice with extra copies of a gene called NR2B, which codes for a receptor on the surfaces of neurons. Specifically, the receptor controls the brain's ability to associate one event with another in memory. Its function normally declines in adulthood, but the extra NR2B genes were set up to increase expression as their owners aged, giving the mice anatomically childlike brains throughout life, with boosted object recognition, spatial and emotional memory and significantly decreased learning times. The mice were playfully--yet somewhat creepily--named Doogies, after the child-genius TV character Doogie Howser. But the "real" Doogie was a doctor, not a rodent--just how smart do we want our household vermin to be?
The goal of this research is not, of course, to breed a race of genetically superior über-rodents bent on global domination; the mouse genome is about 80% identical to our own, so most of these findings have direct bearing on the human condition. Andrew Niccol's 1997 movie Gattaca provides an excellent glimpse at a possible future for this technology: the wholesale engineering of nearly all human embryos for specific physical and behavioral characteristics. This of course presupposes that we know which traits are valuable and which ones we should leave on the cutting room floor. There's a high-stakes gamble for you.
More immediately, these mouse genes may help us design pharmaceutical proteins to control very specific aspects of human health and mood. In fact, they're already doing so; the process of exhaustively collecting and testing natural compounds for possible medical effects will soon be a relic of the 20th century. Believe it or not, by the end of this decade many of these therapies may also be available through tailored viruses that inject them directly into your genome. In fact, research into "regulated promoters" may allow us to insert genes into specific regions of our bodies--say, the abdominal muscles-- and turn them on and off at will with special trigger chemicals. "Body sculpting" may soon take on an entirely new meaning; brain sculpting, too. We can certainly expect the black market to do a brisk business peddling weight loss, genius and brawn, and who knows, maybe self-refreshing tattoos and extra limbs.
One has to wonder, though; with real, full-sized, nonfunctional "dorsal ears" being a serious adornment option for the near future, will body radicals be squeamish about getting them pierced?
Wil McCarthy is a rocket guidance engineer, robot designer, science fiction
author and occasional aquanaut. He has contributed to three interplanetary
spacecraft, five communication and weather satellites, a line of
landmine-clearing robots, and some other "really cool stuff" he can't tell
us about. His short fiction has graced the pages of Analog,
Asimov's, SF Age and other major publications, and his
novel-length works include Aggressor Six, the New York Times Notable
Bloom, and upcoming The Collapsium.
