“Birth defect” written in a typeface created out of chromosomes by Studio Lennarts & de Bruijn for proto.life.

The Language of DNA Should Rewrite English, Too

Jargon from the pre-genomics era blinds us to new possibilities.

Translation is the process of converting one language to another. In biomedicine, it means something less literal: it’s when scientific advances — new diagnostics, therapies, methods — translate into clinically meaningful tools that improve human health.

But words and metaphors matter in medicine, and during a period of rapid change, the evolution of a lexicon can be as important as the underlying science. We’re in such a time now. The genomics era is upon us, which makes pre-genomic jargon increasingly unhelpful. We use old vocabulary out of habit even as the letters of our DNA illuminate new ways forward.

Take, for example, the term birth defect, which is the subject of Imperfect Pregnancies, a 2017 book by Ilana Löwy, a French health researcher. A 2015 Centers for Disease Control and Prevention report defined birth defects as including “congenital malformations, congenital deformations and chromosomal abnormalities,” and it attributed 20 percent of infant mortality to such birth defects. The CDC’s definition captures conditions ranging from small head size (also known as microcephaly, a major fear during the Zika epidemic), to a hole in a heart wall (made infamous by Jimmy Kimmel’s son, Billy), to Down syndrome (caused by an extra copy of chromosome 21). These are all things detected in a newborn or during a pregnancy, through methods such as ultrasound imaging or blood tests for chromosomal abnormalities.

Importantly, the sorts of conditions in the CDC’s definition of birth defects do not include a slew of severe genetic diseases that affect tens of thousands of babies and children each year. One such disease is Tay-Sachs, a horrible condition that destroys nerve cells, killing most affected children before they would have entered elementary school. And yet, a baby born with Tay-Sachs appears physically normal for months or years; his chromosomes, too, appear normal. This is because Tay-Sachs is a monogenic disease, arising out of a single gene mutation, best diagnosed using next-generation sequencing technology. It does not come up in ultrasound or chromosomal analysis.

It would be folly to ignore the ways that genomic medicine can free babies of predictable, devastating genetic diseases.

But while the CDC doesn’t describe Tay-Sachs as a birth defect, it’s the kind of thing cutting-edge commercial genetic testing companies have in mind when they use birth defects in their marketing materials. These companies are specifically talking about deadly monogenic diseases like Tay-Sachs.

How to make sense of these different uses of a common term? Should genetic testing companies use a different word for deterministic monogenic defects than the one for anatomical defects with uncertain prognoses?

These sorts of questions are not mere semantics, because the way that we name different conditions affects standards of medical care, as well as our perception of the conditions themselves. That is, birth defect carries conscious and unconscious associations that could hamper the adoption of new tools designed to detect, treat, and most importantly prevent genetic diseases such as Tay-Sachs. Unlike microcephaly and other defects that are not detectable until a pregnancy is well underway, a monogenic disease is often predictable with genetic screening of the parents, rendering it preventable through one of several options.

One such option is preimplantation genetic diagnosis (PGD), which screens embryos created through in-vitro fertilization (IVF) and implants only those without the disease-causing mutation. IVF-plus-PGD saves thousands of lives, and could save many thousands more; but it is expensive. More clearly describing Tay-Sachs as a preventable disease rather than as a defect will shape physicians’ thinking about recommending procedures like IVF-plus-PGD and influence how insurance companies pay for them.

“Public health,” by Studio Lennarts & de Bruijn.

If overuse of the term birth defect might be slowing down genomic applications, then our definition of public health is also due for a rethink. Löwy distinguishes between “public-health-oriented” and “autonomy-oriented” forms of prenatal testing. Screening for HIV or hepatitis is in the first category, screening for a genetic abnormality is in the second. Her historical review is intriguing, but this distinction reflects a pre-genomic worldview, and today we are due for a change in the way we speak about public health. Genomics represents the shared inheritance of a family and of a community, and so genomic health ought to become public health.

Expanding the definition of public health to include monogenic diseases would be meaningful because of the ways that public-health challenges galvanize innovation and collaboration across the private, public, and philanthropic sectors. While public and private capital has poured into research on the genetics of cancer — long touted as a public health priority — the pace of innovation for programs tied to rare disease genetics has been slower. Monogenic diseases aren’t so rare when pooled together, but compared to cancer or HIV, the emotional and economic burdens of monogenic diseases still feel more like isolated concerns for an unlucky family than shared costs for a community.

Imperfect Pregnancies straddles a tectonic shift in the field of family medicine. As it tracks the study of birth defects and pregnancy screening over the course of the 20th century in Europe and the U.S., the book helps us recognize the paths that led to our current assumptions. From here on out, though, more precise language can alter the paths forward. It may be a fool’s errand to pursue a perfect pregnancy as measured by ultrasound and chromosomal analysis, but it would be folly to ignore the ways that genomic medicine can free babies of predictable, devastating genetic diseases. We shouldn’t let promising innovations become lost in translation.

Lee Cooper, a lawyer and health care entrepreneur, is founder of the Institute for Genetic Disease Prevention, a nonprofit organization focused on patient advocacy and education.

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