Consider the Fruit Fly

Modern genetics would not be possible without the humble fruit fly.

In college, I worked briefly in a fruit-fly lab, where I spent most of my time just keeping different fly strains alive. It was not difficult—as anyone with a fruit-fly infestation can tell you—but the repetitive work imprinted itself on my brain. Even today, the way my slightly chubby white cat scrunches when he walks resembles nothing more to me than a third instar fly larva, swollen and ready to metamorphose.

This is to say that I came to First in Fly, a new book about fruit-fly research, with perhaps some special interest. In fact, a popular appreciation of fruit flies has seemed long overdue to me. No single animal has contributed as much to the field of genetics as the ordinary and ubiquitous Drosophila melanogaster.

These tiny, winged, exoskeleton-ed creatures—so different from us in appearance—have led to research illuminating a surprising amount about the human body: The genes that tell a fruit fly where to sprout its legs are quite similar to the ones that tell our bodies where to sprout limbs. As are the genes that form the pattern of fine hairs on a fly’s wing and the ones that orientate the tiny hairs in our ears. As are the genes that govern a fruit fly’s circadian rhythm and the ones that give us jet lag. And so on. Research into Drosophila has resulted in at least five Nobel Prizes.

First in Fly by Stephanie Elizabeth Mohr is a thorough chronicle of the contributions of these creatures to science over the past century. Mohr herself is a fly scientist at Harvard Medical School, and she knows intimately the life of a “fly pusher.” (The name comes from the act of pushing flies around under a microscope.) She can at times drift too far into molecular biology for a lay reader, but her book is at its best when it conveys both the ingenuity and sheer labor necessary to coax biological secrets out of Drosophila. If you’ve ever looked at a fly and wondered what it could possibly tell you about the workings of the human body, well, it’s not easy for scientists either.

Harvard University Press

Consider the story of the gene memorably named Sonic hedgehog. In the 1970s, Christiane Nüsslein-Volhard and Eric Wieschaus in Heidelberg, Germany, were studying a topic that probably sounds hopelessly trivial: patterns in the cuticle, or the protective outer layer, of fruit-fly larvae. They performed what is called a “forward genetic screen”—in which tens of thousands of male fruit flies are fed a chemical that induces mutations and then individually mated with a female. Nüsslein-Volhard and Wieschaus then spent a year sitting side by side at the microscope, looking for individual mutants with unusual cuticles. “Performing a screen,” writes Mohr, “is often an endurance event.”

It paid off. Nüsslein-Volhard and Wieschaus found 15 mutations that resulted in odd-looking cuticles. One of them, which made the cuticle short and spiky, they named hedgehog.

Humans, it turns out, have versions of the hedgehog gene—three, in fact, derivatively named Indian hedgehog, desert hedgehog, and Sonic hedgehog. In fruit flies, the gene coordinates the body plan of the larva, which is manifested most clearly in the unusual shape of its cuticle when the gene is disrupted. In humans, it serves a similar function, telling the embryo which way is front and back, left and right. Babies with mutations in Sonic hedgehog are born with brains that lack distinct left and right hemispheres. So important is the Sonic hedgehog gene that its name has become controversial. What doctor wants to tell a new mother that her gravely disabled child has a mutation in the Sonic hedgehog gene?

Because so many genes have been discovered in Drosophila, many bizarre names originate with the behavior or appearance of the flies. You can imagine how in the drudgery of fly pushing, scientists might dream up fun names for new genes. Some of the most memorable ones in Mohr’s book include:

  • cheapdate: Discovered in fruit flies that are, well, especially sensitive to alcohol
  • hippo: Discovered in fruit flies with huge heads and wrinkles around their necks. In fruit flies and mammals, it controls the size of organs.
  • Van Gogh: Discovered in fruit flies with a “whirling pattern of orientations of the wing hairs, reminiscent of the whirling lines typical of the eponymous artist’s paintings,” writes Mohr. In mammals, a version of it is responsible for the development of hairs in the inner ear.
  • ether-à-go-go: Discovered in fruit flies whose legs twitch rhythmically when anesthetized with ether. In humans, a version of it codes for part of the potassium ion channel that coordinates the heartbeat.
  • spätzle: Discovered in fruit flies whose larvae are irregularly shaped like the German noodle. In fruit flies, spätzle makes a molecule that binds to Toll proteins, named after Christiane Nüsslein-Volhard’s expression “Das ist ja toll!” (“That’s amazing” in German.) Toll proteins are involved in immunity in both fruit flies and humans.

The imaginative gap between these gene names (based on the purpose they serve in fruit flies) and their function later discovered in humans makes obvious just how difficult it can be to anticipate the relevance of fruit-fly research beforehand. In total, Drosophila melanogaster has 14,000 genes, 8,000 of which have human analogues. To read First in Fly is to appreciate the full scope of fruit-fly research and to understand the intimate connections in the DNA of every human cell and Drosophila cell.