What Yeast and Beast Have in Common

Genetics has come a long way from the humble monk Gregor Mendel and his quiet experiments with cross-breeding garden peas. In the hundred and 10 years since Mendel's death, the heuristics of heredity have exploded. We're in the midst of a genetic revolution, one that inspired Nobel-prize winner Renato Dulbecco in 1985 to make a public plea for the now highly publicized—and criticized—Human Genome Project, which forecasts that by the year 2005 every gene in the human genome (genome refers to all the genetic material contained in the chromosomes of an individual) will be mapped out. Every week, it seems, the newspapers carry stories of the discovery of new genes (many discovered by researchers not working on the Human Genome Project). In the first month of 1994, we were told about the isolation of genes responsible for colon cancer, bone disease, and human embryonic development. The narrative of genetic odyssey even made the cover of Time magazine.

An issue recently debated in the popular press, the cloning of humans, gave rise to the unfortunate impression that our genetic advances have led our society into an Orwellian nightmare, or a chapter from The Boys from Brazil in which author Ira Levin creates a cadre of Hitler clones.

For all the work done in the fertility field—yes, the human embryo can be split into identical twins or triplets—research into genetic manipulation of germ-line cells (the sperm and egg) is still banned in this country. And for all the talk about "designer children," the technology to produce a perfect child simply isn't there. "If we could figure out how to control a gene as banal and uninteresting as making a kid's hair blond," Abmayr says, "we could figure out how to cure muscular dystrophy."

The more relevant ethical questions for Abmayr concern genetic testing. Pregnant women today can request genetic testing early in their pregnancy, around the 16th week, capable of detecting close to 70 diseases and chromosomal disorders. Amniocentesis, blood and cell tests, alpha-fetoprotein testing and chorionic villi sampling can predict the presence (or lack) of the chromosome commingling that results in a number of diseases—Down's syndrome, cystic fibrosis, Huntington's chorea, spina bifida, Tay-Sachs disease, Duchenne's muscular dystrophy. Perhaps in the next millennium, science will not only have better tests, but better in utero treatments for the 4,000 known single-gene defects that can afflict the human condition.

"Ethical questions are raised by our ability to detect but not correct genetic diseases," says Abmayr. "I think we as scientists have a responsibility to educate the public about the real issues."

What Yeast and Beast Have in Common

"At our last meeting," says Ross Hardison, director of Penn State's Center for Gene Regulation, "I strolled over to see one of our new members, Esther Siegfried. She was talking up a storm with June Medford and Susan Abmayr.

"They were talking about 'Hedgehog.'"

Siegfried, a new faculty member shared by the biology departments and molecular and cell biology, works with fruit flies, as does Abmayr, who hails from the department of molecular and cell biology. Medford is a biologist who studies plant cells. The "Hedgehog" they were discussing was work recently done at Harvard Medical School with a group of genes that can make a fruit fly mutate into a bristly hedgehog-looking shape.

"And they were really excited about it," continues Hardison, "tying it in to some old ideas about morphogens. After a while, it started relating to something I understood."

Hardison stops, spreads his hands for emphasis. A biochemist, he studies the genes that control the making of hemoglobin in mammalian cells.

"That's one of the things that keeps coming around to us here at the Center: that there are some fundamental paradigms to gene regulation whether you're working with bacteria, fungi, plants, or animals.

"And the more we learn the more parallels we see.

"It shouldn't be a surprise, really, to those of us who think at the molecular level," he continues. "Genes have been regulated and been expressed since the earliest cells. It shouldn't be surprising that they have things in common.

"Yet this understanding was not at all clear before the mid-1980s. The textbooks are only just starting to catch up."

Penn State's Center for Gene Regulation began three years ago, following the informal realization by three assistant professors in molecular and cell biology (Andrew Buchman, David Gilmour, and Tracy Nixon) that the gene regulation systems they were studying—in yeast, fruit flies, and bacteria—were in some ways the same.

The Center was formally established last year, combining 18 faculty from four departments in two colleges (the Eberly College of Science and the College of Agricultural Sciences). The members' genes of interest reside in bacteria, viruses, yeast, fruit flies, plants, mammalian cells, and in the euphonious "cell-free system." (Says Hardison, "A cell has a very complicated background. There's a limit to the resolution you can get. So what biochemists love to do is to break open the cell and pull out just the things we're interested in.")

Members of the Center share equipment, submit common applications for training grants and the modernization of facilities, serve on the dissertation committees of each others' graduate students, and act as a core for recruiting new faculty.

"But the heart of the Center," says Hardison, "is the biweekly meeting. Getting feedback, getting riddled with questions . . .

"It's mostly the graduate students who present the research," he says, adding, "in our departments, the bulk of research is done by the graduate students. And it's mostly a friendly atmosphere. We're all working together as a team to do something significant.

"Although we work with diverse systems, at a molecular level, there's a common paradigm." Hardison laughs, drops his voice. "It's called a paradigm," he adds in an aside, "when you don't know the actual molecules involved."

Ross Hardison, Ph.D., is professor of biochemistry in the Eberly College of Science, 206 Althouse, University Park, PA 16802; 814-863-0113.

Last Updated June 01, 1994