Dan Lindsley pauses for a moment when asked to give the names of his favorite mutants. Well, he says, there is Drop Dead. And Coitus Interruptus. And Male Chauvinist Pigmentation. But there are so many to choose from.
About 4,000, to be exact, and Lindsley knows them all.
As professor emeritus in the biology department at UC San Diego, Lindsley has spent much of the past decade cataloguing all the mutant genes identified in the fruit fly Drosophila melanogaster-- genes with such improbable names as Dunce, Rutabaga, and Killer of Prune.
The encyclopedic work, co-authored by UC San Diego biologist Giorgianna Zimm and soon to be published by Academic Press, is intended as a technical reference, condensing nearly a century of research by hundreds of scientists who have used fruit flies as model organisms for basic studies in genetics. But it also provides a candid look at fruit fly geneticists, who are, it turns out, a rather droll lot, and who channel much of their talent into the creation of clever names for the genes they discover.
To be sure, weird humor is a hallmark of most scientists--a manifestation of their hunger for a measure of caprice in a line of work that, in its day-to-day execution, is monotonous and frustratingly prone to failure. But fruit fly geneticists have a reputation for an extra measure of wackiness.
They point proudly to a history of deviant behavior dating back to Thomas Morgan, the turn-of-the-century naturalist and Nobel laureate who not only studied fruit flies but ate them as well. And they take pains to distance themselves from scientists studying the tiny nematode, or roundworm, known as C. elegans --the second most popular model organism among geneticists.
Nematode watchers adamantly refrain from assigning funny names to the genes they discover and accuse fruit fly workers of going so far as to invent names they want to see in print, then spending years in search of mutant flies with deformities or behavioral traits appropriate to those names.
That has been known to happen, concedes Thomas Kaufman, an Indiana University fly geneticist. But a gene name must be more than funny. "To work, it has to have a rationale," he said in a recent interview.
Burke Judd's story is typical. A fly geneticist at the University of North Carolina, Judd discovered a faulty gene that leaves fruit flies intensely sensitive to shocks; a simple shake of the glass container housing these flies leaves them stunned and flat on their backs for several minutes. Scientifically speaking, the gene controls tiny channels that regulate salt concentrations inside cells.
But never mind all that. Judd named the gene Technical Knockout, and in scientific journals and among those in the know, the gene is now referred to as TKO.
Another mutant gene, which malfunctions only at low temperatures and knocks flies unconscious whenever the mercury dips below 76 degrees Fahrenheit, is named Out Cold. And then there is the gene that acts like a time bomb in the brain, causing sudden neurological degeneration in seemingly healthy flies. "One minute they're walking around, then all of a sudden they just topple over," said Lindsley. The gene, discussed in earnest at scientific meetings, is known as Drop Dead.
Some gene names invoke musical, literary, or historic reference. A gene that leaves young flies unable to develop into adults goes by the name Oskar, after the perpetually youthful dwarf in Gunter Grass' "Tin Drum." Trudy Schupbach at Princeton has named several genes--all of which cause sterility in female offspring--after European royal families such as Tudor, Valois and Vasa, whose reigns were cut short because of maternal sterility. And at least one fruit fly mutation embodies a biblical reference: Flies bearing a gene called Lot can drink salt solutions 10 times more concentrated than the saltiest drinks accepted by normal flies.
Names like these do not arise among geneticists studying the nematode C. elegans . Without exception they give each newly discovered gene a three-letter code, sometimes followed by a number. Unc-1, unc-2, and unc-3 are representative--a dour legacy that has spawned widespread derision from fruit fly geneticists. "You can't dynamite an interesting name out of a nematologist," said Jeff Hall, who studies Drosophila at Brandeis University.
Others put the blame on Sydney Brenner, the British father of worm genetics, who in the 1960s first proposed using C. elegans as a model organism for genetic studies. "We're not going to call our mutants things like Apricot," Hall recalls Brenner saying at a genetics conference in the 1970s.
But, for the most part, the feud between worm geneticists and fly geneticists is personal. "I have to say, worm people seem to lack a certain spark of imagination," said UC San Diego fly geneticist Michael Levine, adding that his impression is that they are "bright but nerdy."
Indiana University fly researcher Thomas Kaufman is less diplomatic. "Worm geneticists," he said flatly, "are sticks in the mud," incapable of appreciating the beauty of such genes as Coitus Interruptus, which programs afflicted flies to mate for a mere 10 minutes instead of the usual 20, or another gene, called Stuck, which causes an opposite sort of problem that need not be described here in detail.
The roots of this fanciful system can be traced to Morgan, who taught zoology at Columbia University. By the time he began studying fruit flies in the early 1900s, Morgan's work with sea urchins, squid and other marine organisms was widely renowned--in part because of his habit of eating those specimens after completing his experiments. One could never really know one's experimental organisms without consuming them, he claimed.
Starting with a white-eyed mutant lured to his lab by an overripe banana, Morgan began a series of breeding experiments that confirmed the presence of a gene for eye color and heralded the birth of fruit fly genetics.
Culinary experimentation continued as well; in keeping with his philosophy, Morgan snacked on partially metamorphosed fly pupae and told his co-workers that they tasted like Grape Nuts, which have been around since the turn of the century, according to Post cereal officials.
Morgan showed apparent restraint by giving that first gene the simple name White. But in choosing a name that described in plain English the mutant trait, rather than employing some scientific jargon, he inadvertently began a tradition that would guarantee the use of more outlandish names later on.
As additional eye-color mutations came to light, fruit fly geneticists discovered in themselves a well of creativity seemingly more appropriate to Crayola consultants, adding Apricot, (sorry, Dr. Brenner), Amethyst, Vermilion, Cinnabar and Prune to the Drosophila vernacular. A mutant gene that is lethal to flies with prune-colored eyes is named Killer of Prune.
In the 1960s and '70s, as scientists discovered mutant flies with more complex abnormalities, things got more out of hand. In 1971, Seymour Benzer at Caltech discovered the first inherited learning disability in Drosophila . Normal fruit flies, while not brilliant, can learn to avoid electrical shocks. Benzer discovered a strain of fruit flies unable to master this avoidance response, found the faulty gene and named it Dunce.
At least one gene that seemed initially quaint was re-christened years later because of changing social and political sensitivities. Back in 1963 a Yale University researcher named Kulbir Gill discovered a mutant gene that induced male fruit flies to engage in courtship behavior with other males. Gill named the gene Fruity.
By the 1970s, times had changed. Hall contacted Gill to discuss a name change for the gene, and together they came up with an elegant solution. They renamed the gene Fruitless--an appropriate moniker considering the lack of mating success or offspring among these mutants, and one that allowed continued use of the three-letter abbreviation, fru, which had already become common in the scientific literature.
The mcp gene is a another period piece. Identified by Lynn Crosby, now at the University of Minnesota, it causes a tiny splotch of pigmentation to extend beyond its usual boundaries on the abdomens of male flies, but has little or no effect on female coloration.
In the '70s, Crosby informally christened the gene Male Chauvinist Pigmentation and gave it the abbreviation mcp. But as it came time to describe the gene in a presentation at a national conference, her laboratory chief balked at the prospect of formally establishing the politically charged name. After a week of brainstorming with colleagues she struck a deal with the chief, retaining the abbreviation mcp but having it stand for Miscadastral Pigmentation--from cadastral, a surveyors' term referring to boundaries.
Although fly researchers are for the most part a gentle lot, competition for clever names can get surprisingly fierce. On several occasions researchers have spent months or years studying and naming a gene, only to learn that others have scrutinized the same gene and named it something else. A battle of endurance generally follows, in which each team publishes as many papers as possible using its gene name, with the hope that it will be accepted by the scientific community.
Opposing parties have in some cases forced Lindsley into the unenviable role of a Drosophilan Solomon.
"I had a big argument about Serrate," Lindsley said, referring to a recently described wing-deforming mutation that turned out to have the same genetic basis as another, named Beaded, first identified in 1914. "And not everybody is going to be happy about my acceptance of Decapentaplegic"--a new name, first proposed and actively lobbied for by Harvard University's William Gelbart, for a single mutation that causes fifteen defects in fruit fly appendages. The gene had been given many different names over the years by researchers who had studied its various manifestations.
"I've tried to be diplomatic, but a lot of people are going to be upset about some of these decisions," Lindsley said. "It's good you decided to call now," he added. "Once the book comes out, I'm just not going to answer my phone."
An Endless Variety of Mutants
Variations in wing shape, wing vein patterns and so on have been the focus of nearly a century of genetics experiments with the fruit fly Drosophila melanogaster , and have inspired fruit fly geneticists to stretch their imaginations and their senses of humor in their search for descriptive names for the genes that cause these traits.
Among the many wing shape mutations are Curled, Curly, Curvoid, Curvyoid, Warped, Rotund, Fluted, Scalloped, Serrated, Crumpled and Wavy.
With the more recent discovery of mutations that cause unusual behaviors, the names given to the genes are becoming not only humorous but also increasingly anthropomorphic.
Source: Adapted from "Genetic Variations of Drosophila Melanogaster," by Dan L. Lindley and E.H. Grell
Names That Tell It All
Here are some examples of colorful names given to mutant genes of fruit flies:
Technical Knockout (TKO)--This gene leaves fruit flies so intensely sensitive to shocks that a simple shake of the container housing them leaves them stunned and flat on their backs.
Out Cold--The gene knocks flies unconscious when the mercury dips below 76 degrees.
Coitus Interruptus--Programs flies to mate for a mere 10 minutes instead of the usual 20.
Male Chauvinist Pigmentation (MCP)--The gene causes a tiny splotch of pigmentation to extend beyond its usual boundaries on the abdomens of male flies, but has little or no effect on female coloration.
Lot--Biblically inspired name of a mutant gene that enables flies to drink salt solutions 10 times more concentrated than the saltiest drinks accepted by normal flies.