Something like that sentiment echoed in another field when news of the first human artificial chromosome, or HAC, surfaced in 1997. It was created by a team at Ohio’s Case Western Reserve University, led by the geneticist Huntington Willard and working with the Athersys corporation. The HAC was successfully taken up by a single human cell and passed down through 240 generations.

The human genome is contained in twenty-three pairs of sausage-shaped units called chromosomes. At the heart of every chromosome is a double-helix strand of DNA twirled around ball-shaped proteins called histones. Then the whole business is wrapped in a shell of chromatin—still more protein. The Case Western replica was roughly a tenth the size of a typical human chromosome. When it was placed inside a nucleus, it was welcomed into the natural sequence of chromosomes and wrapped up in chromatin. Melissa Rosenfeld, speaking at the time for the National Human Genome Research Institute, described the effort as “an important landmark.”

When evolution tries out a mutation that seems to reduce fitness, it’s labeled a genetic disease. Some of them are terrible, and we have good information on the causes. But to insert therapeutic genes requires a delivery system that the nucleus will accept. Until now the available vectors—modified viruses—have been so dangerous and imprecise that it’s had a restraining influence.

All this changes with HACs. They are larger than viruses, and so can carry bigger genetic payloads. They aren’t inserted in the body’s DNA but are added on, as a separate chromosome. They are less likely to provoke immune reactions. And they don’t have to be “disarmed,” as viruses do, so there’s no risk that the disarming might fail and cause a serious disease or even death. The availability of HACs as a safer delivery cart will mean a steep rise in the number of attempts at gene therapy. That has profound implications. Beyond concerns over modifying a fundamental system that we don’t fully understand, the deeper issue HACs raise involves the ease with which they can permanently alter the human gene pool.

Germ-line cells are sperm and eggs. As they combine and grow into the earliest stage of an embryo, the body sets aside the cells meant to make more sperm and eggs—directing them along a line that is separate from those other cells that grow into organs in the expendable body. This is August Weismann’s famous barrier between cells for making babies and those for making bodies. The genetic modifications that are allowed today are made to cells that have already passed through Weismann’s barrier. Since they will only grow into body parts—skin, a heart, an eye—the results from any modification are contained within that body alone. But germ-line cells are for reproduction; genetic changes to them will be inherited by offspring. HACs increase the plausibility of engineering the germ line.

As with directed evolution, even though the implications here are radical, there is strong support for doing it. Most of that support focuses on health issues. In dealing with a genetic disease, for example, the advantages are clear. Where there is reason to suspect an inherited disease, instead of having to treat all the cells affected in an adult organ, doctors can head off the culprit at its source. Responding to one science magazine straw poll, a group of gene researchers described human germ-line engineering variously as “‘irresistible,’ ‘morally questionable,’ or ‘dangerous.’” But they all agreed that “germ-line engineered humans are likely to become a reality.” Gregory Stock, a UCLA biophysicist and outspoken proponent, claims the technology is unavoidable. The prospects, he says, are simply too bright. In his book Redesigning Humans, he describes a future in which parents pick their children’s features as they would options for a new car. Far from discouraging germ-line modifications, Stock argues, we should manage them in a “free market environment with real individual choice, modest oversight, and robust mechanisms to learn quickly from mistakes.”

There’s little question that HACs could allow the loading of customized gene sequences into human germ-line cells. There is even speculation about building in genetic “switches” that would be activated only in specific tissues, or by a drug the patient takes later. Some historical perspective is in order here, involving the “Beltsville pig”—or No. 6707, as he was known to the USDA researchers who created him. The animal was genetically engineered some years ago to produce human growth hormone that would make it grow faster and leaner. The result of that work, according to Andrew Kimbrell in his book The Human Body Shop, was “a tragicomic creation. Excessively hairy, lethargic, riddled with arthritis, apparently impotent, and slightly cross-eyed, the pig could hardly stand up.” The engineers had spliced in a switch intended to activate the hormone only when the pig ate large amounts of zinc. The switch failed.

Tags: Beltsville Pig, chromosomes, DNA, double helix, gene therapy, genetics, HAC, human genome, Stock, Willard

Email this to a friend | Add to del.icio.us | Add to digg |
Linkology by Kate (all links are unofficial) | Rights Info

Rating: 4, from 1 votes

Posted on April 28th, 2006 @ 3:00 pm