Light in the Darkness

New Finding That Testing Could Identify Defects in Fetuses Is a Baby Step for Genetics

Researchers say they can ID “point mutations” that might lead to abnormalities, but it is a baby step forward in genetics, says Kent Sepkowitz.

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Genetic defect is perhaps the most frightening term any new parent can hear. In the United States, about 1 percent of all newborns have discernible genetic defects ranging from the well-known, such as Trisomy 21, or Down Syndrome, to the obscure, such as ichthyosis. One of the goals of the still-new field of genetic medicine is to be able to identify these defects at an early time and enable the parents to decide about the pregnancy, as with Down, with the dream that someday, hopefully soon, some sort of genetic “patch” will be devised that can fix the problem before the baby is even born.

Substantial progress on this front was announced this week in the medical journal Science Translational Medicine, and reported widely, including in The New York Times. The researchers were able to cobble together almost the entire genetic sequence of a fetus without a direct sample from the fetus itself. They also showed that they could identify most of the “point mutations”—those genetically abnormal spots, aka genetic defects, along the spiraling double helix—that might lead to clinical abnormalities.

The novelty of the work is that it gathers critical information from a blood test from Mom (which contains good amounts of cell-free DNA from the fetus) and a saliva test from Dad—but nothing directly from Junior. The information gathered previously has required invasive methods, such as chorionic villous sampling, or CVS, which involves a biopsy of the placenta. This procedure, though generally safe, comes with a small risk of complication, including loss of the fetus. The better-known approach, amniocentesis, must be performed later in the pregnancy, meaning that, should an abnormality be found, decisions about termination must be made in a more compressed time frame. In addition, it too can be complicated by fetal loss and other problems.

Each of these scientific advances represents a remarkable achievement for the generation that spawned it—amnio in the 1950s, CVS in the 1980s, and the current genetic high-wire act just this week. And each has and promises to allow parents to make rational, if sometimes extremely painful, decisions about their family. Yet they also have created an enormous—really enormous problem: the excitement of inventing the tool, trying it out, and solving the puzzle has generated such scientific momentum that each has barreled headlong into a morass of impossibly complex ethical and spiritual issues without sufficient pause. As such, scientific information once again has gotten way out front of the clinically practical. What does it mean, really, if your 14-week-old fetus has a deletion on chromosome 12? No one has a clue, probably, but you’ll still be scared senseless (though the fear may recede by the child’s 30th or 40th birthday, I promise).

And tight-lipped, buttoned-up groups like the Seattle researchers involved in the latest step forward are only a small corner of the problem. Venture capital and insatiable self-interest—always a toxic mix—have teamed up once again to give us home DNA kits, a simple-ish 1-2-3 DIY that promises to allow users to get to the bottom of their DNA and therefore sort out their destiny. It’s today’s Delphic oracle, but without sibyls, weird noises, or trudges up the mountain. Of course, it also comes with complete ignorance about the implications of anything abnormal you might find (as well as awful reproducibility), but offers that intoxicating whiff of the future bundled up with a sense of controlling your own destiny. I know my DNA, therefore I am.

Well no, not really. The Watson-Crick generation(s)—starting with the Baby Boomers and working on through whatever catchy term they are calling the gang born this century—has exhibited a bedrock belief in the indivisible, superseding, overarching, immutable truth of DNA. It is our atom, our monad, our only terra firma. Yet it is kind of a dud, no? I mean, here we are 60 years after the double helix was described and 20 years into the Human Genome Project, and what have we got? Here’s what: a thousand, nay ten thousand new academic medical careers, a flood of complex medical articles on this mutation and that, a patent or two, and a truly exciting first-pass understanding of the genetics of cancer. Only the latter has borne real fruit, though surely next year or next decade additional gains will be realized and slow, steady inroads made into countless other diseases.

But the dream was really different. When first genomics started, we figured the result would be self-improvement—literally. Our self, our DNA self, would be smoothed down and spliced up to a new better us; that the gene for social awkwardness and saying stupid things to beautiful tall women, for example, would be removed, and that for being a big quarterback dude who played electric guitar too would be spliced right in. And our vision would improve and our teeth and even that urge for an extra 15 minutes of sleep every morning. We would be improved and wouldn’t have to do anything much to accomplish it except maybe go to the doctor and have an intravenous or something.

The Seattle group leading the latest DNA revelation is to be applauded for making another baby step forward, for adding a tiny light to the vast darkness of 21st-century science. But their accomplishment is less the promise of developing a new way to detect genetic defects than a reminder of the incredible complexity, uncertainty, and glacial pace of scientific progress. This team of esteemed researchers, working for months was able to sort out the genetic composition of two mother-father-fetus sets in a matter of months, with good but not perfect accuracy. Next year, the group hopefully will add a bit more to the story. But for those of us looking for a shortcut to better hair and a longer life—I’m afraid we’re still stuck with our same old boring DNA.