What's the Buzz?

By Georgette Weir

As do most of us, Nancy Pokrywka swats at houseflies. She flails at mosquitoes that sing round her head. She escorts to the outdoors spiders who get cozy in her corners. But fruit flies at her bananas? Pokrywka, a developmental biologist at Vassar, knows them too well and admires them too much to do other than extend a welcome. She declares herself a "fruit fly bigot" and asks in exclamation, "What harm do they do?" Indeed, as Pokrywka (pronounced Po-kref-ka) makes clear in conversation, what good they have done.

The fruit fly has been called the "Rosetta stone" for deciphering the human genome. These subjects of nearly a century’s worth of studies have yielded much that we know about genetics. Perhaps most startling, they have revealed extensive overlap in the genetic material of very diverse organisms—flies and humans, for example. As much as 30 to 40 percent of the fly genome may also evidence itself in the human genome, says Pokrywka.

The discovery of this genetic overlap suddenly made much fly research directly relevant to humans. The commonalties are such that we can study the fly and learn about human diseases; we can study the fly and learn about human cures; we can study the fly and get clues to the processes of our own embryonic development; we can study the fly and find pieces of the puzzle of the history of life on earth; we can study the fly and simply respond with awe at the complexity of a tiny creature we squish without a qualm. Fruit flies and humans may occupy different branches of the family tree, but, genes tell us, family we are.

Fruit flies, mere specks to our unaided eyes, are marvels of complexity. Each fly has four pairs of chromosomes, 165 million bases (the ingredients of DNA) that make up an estimated 14,000 genes. For comparison, an Internet directory for Drosophila (http://ceolas.org/VL/fly/intro.html) notes that the human genome has an estimated 3,300 million bases and may have from 50,000 to 70,000 genes; in yeast, a single-cell organism, some 13.5 million bases comprise about 5,800 genes.

Drosophilia is a species with which anyone who has taken a class in introductory biology or genetics has at least a passing acquaintance. For the better part of the 20th century, it was the model organism used to research and teach genetic inheritance. Its small size, quick life cycle,and ease of crossing, raising, and handling make the fruit fly ideal for the lab.

Taking advantage of these features, Drosophilists (it sounds like a cult but Pokrywka calls it a community of several thousand scientists world -wide) have been at the forefront of the science of genetics. They also led the way, beginning in 1910, in the study of inheritance by focusing on natural mutations in flies. They led the way in deliberately introducing genetic mutations, through X-rays, then, through observation, connecting specific mutations to physical characteristics, behaviors, and development. By the early 1970s, says Pokrywka, so much had been learned about fruit fly genetics that people were saying the field was dead. "We had learned what genes are, we had learned how chromosomes behave, we had learned how mutations are made, and the usefulness of the fly had pretty much reached its limit." Then, in the mid 1970s, two researchers using new chemical techniques to induce and study mutations systematically revealed "hundreds and hundreds of mutations" that affected the development of a fly. They not only revived the study of Drosophila, says Pokrywka, "they have pretty much changed the way people think about developmental biology." The impact and workings of genes suddenly became the central focus.

Nowadays, developmental biologists seem to research everything at the genetic and molecular level, from embryonic development to learning to addiction. Pokrywka gives some examples: "Experiments done by Drosophilists were among the first to identify genes that are important for learning. It turns out you can teach Drosophila. You can teach them to avoid certain odors. You can study the acquisition of memory. You can teach Drosophila and then you can wait and see how long they remember what they are taught. And then you can look for mutations—in fruit flies that can’t learn or that learn and then forget. In that way people were able to identify genes that are important for learning—from fruit flies. People are using fruit flies to study the biological basis of drug addiction. You can addict flies to things like cocaine and then study the genes that are involved in habit-forming behavior. People have studied sexual behavior in fruit flies and found some genes involved in the mating behavior and courtship of flies. As far as behavioral genetics, an awful lot has been done. Now we have all these genes that we know [are] in humans that are ripe to be studied."

But the human studies are for others. Pokrywka sticks to her flies. Her own research is a direct outgrowth of the genetic discoveries of the ’70s and ’80s. Working for seven years in a Vassar lab, with funding from the National Institutes of Health and aided by undergraduate assistants, Pokrywka studies a gene that seems to be central to an issue that now consumes many researchers: How does a single-cell egg transform into a complex adult organism?

It is an age-old question that is being effectively investigated only now, at the level of the gene.

Pokrywka’s gene is one in Drosophila called swallow, which, despite its name, has nothing to do with swallowing. Instead, evidence indicates that the swallow gene is important in organizing the contents of the fruit fly egg into top and bottom, front and back—the first and most basic directions in creating any organism. Swallow, explains Pokrywka, "is the stretch of DNA you need to produce the proper gene product in the proper place at the proper time. If molecules don’t get to where they belong [in the egg] the result is aberrant development." How the gene does this is the subject of her study. Three projects are under way in her lab. In one, she changes specific portions of swallow in the test tube, puts that changed gene back into flies, then looks at the flies to see the impact of the change on their ability to make eggs. Another looks at a different gene that is thought to be interacting with swallow. "The idea is, if you can figure out what proteins swallow interacts with, you can figure out how it is getting its job done." In the third project, she and a student assistant are looking for swallow in other flies and insects. The hunch is that swallow may be among the genetic components Earth’s life forms have in common.

Pokrywka admits that her primary research motive is intense curiosity and the satisfaction of being the first to learn something new about her subject. But she also emphasizes that understanding any organism, including fruit flies, can lead to greater understanding of humans. Intimate knowledge of general cell biology has benefits in understanding and treating human diseases. "A lot of the major advances that have been made in treating AIDS and HIV all came out of basic cell biology research," she says by way of example. She repeats often: Discoveries in one organism can aid and abet discoveries in another.

Of course, that very fact also sets off alarms in many quarters. The ethical issues raised or created by some genetic research are increasingly part of our everyday discourse. Pokrywka says her own field of research doesn’t directly deal with such dilemmas, but she acknowledges they are part and parcel of genetic studies. This spring, in fact, she is teaching a course on genetic engineering under the auspices of Vassar’s Science, Technology, and Society program. Her goal, she says, is to give students a basic understanding of biological foundations and techniques of genetics so they can analyze and judge issues with some objectivity. "I hope we’ll be deconstructing some of the black-and-white" that has developed around issues of genetic engineering and that students "will see that there is a lot of gray."

box for flies
box for flies

Inside Pokrywka’s fly lab in Olmsted, shelves line one corner wall with small bottles that seem to have been emptied of chocolate milk and left uncleaned. A closer look reveals the bottles are coated with a yeast-colored nutrient mix and fruit flies in various stages of the life cycle. In some, adults are flying; in others larvae crawl. Pokrywka picks up a bottle of adults and shakes them onto a small disk impregnated with carbon dioxide. The flies are instantly unconscious. She takes tweezers and drops several flies onto a slide, gazes at them through the microscope, and quickly sorts them into three males, two female virgins, and three "experienced" females. What moments earlier were insignificant dark specks are now seen to be complicated creatures with lacy wings and patterns of brown, red, pink, blue, and black. She returns the flies to their bottles. "It’s been a while since I’ve looked at the flies under the microscope," she says, noting that most of her work is on the molecular level. "This reminds me of how beautiful they are."

As she talks about her flies, Pokrywka grows more animated. She describes swallow : the gene is made of about 4,500 base pairs—the famous ingredients of the DNA double helix—and it makes an RNA that is about 2,600 nucleotides long, which makes a protein that is 548 amino acids long, —an "average size protein" —which acts in ways that are still mysterious. She explains lab techniques and speaks with awe about the complexity of life, even at its most minuscule. Despite 100 years during which thousands of labs have studied the tiny fly Drosophila, "we haven’t even begun to understand them," she points out, citing the mysteries of just the swallow gene. "We can say that humans have at least three times as many genes as fruit flies. And we’re not even close to understanding fruit fly biology and fruit fly genetics." Last year’s publication of the first maps of the genomes of both fruit flies (in March) and humans (in June) were major achievements that may nevertheless obscure the mysteries that still exist.

The wonder of it, she admits, is sometimes hard to keep in mind during the day-to-day details of experimental work. But it is that very work that she loves doing—along with teaching—and she says the fact that she is at a small college gives her the freedom to stay active with both. At research-oriented universities she observed that the people who ran the labs rarely did experiments. "They wrote grants, they dealt with bureaucracy and paperwork and reports." At Vassar, she notes, "I’m in the lab almost every day doing experiments and being able to keep my hands right in the thick of things, being at the bench and working with the flies and working with the DNA, doing crosses. That is immensely satisfying."

Pokrywka is unabashed in her enthusiasm for fruit flies. Her Website proclaims "Time’s fun when you’re having flies." Her favorite organism, it cheers, is "Drosophila." The door to her lab sports a Far Side cartoon of a cowboy fly (yes, a fly wearing a black 10-gallon hat and western-style vest—this is Gary Larsen, after all) confronting a barkeep who is reaching for his swatter. "I wouldn’t do that bartender . . ." warns the fly. There are newspaper articles about fly people (researchers) and their work. In the category of hearsay, there is the story of Pokrywka devising and wearing to class a fly costume one Halloween. She gives a combination moan and laugh as she acknowledges this last and brings out what is left of it: a piece of pale yellow fabric with brown pipe-cleaner bristles sticking out all over. "Not only was I a fly," she says, "I was a fly that had the same mutations as what the students were studying in lab. So after I walked into class and the laughter died down, I said, all right, I want you all to identify the mutations that I’m carrying. They looked at me and figured out my genotype from the costume I was wearing." The lesson will no doubt be long remembered by her students.

Pokrywka lobbies hard for her tiny charges. " If you want to understand behavior, you can study Drosophila. If you want to understand how cells develop, you can study Drosophila. If you want to understand simple cell biology questions, you can study Drosophila . . . If you’re going to work on something, you almost have to fall in love with it, and that’s how I feel about my flies. They’re these tiny, beautiful creatures, and there’s all this complexity going on." And they are our very distant relatives, maybe 200 million years removed.

Consider that when you next raise your hand to squish one at your fruit bowl.

For more about Pokrywyka’s research, visit http://biology.vassar.edu/facultystaff/pokrywka.html