Notebook: October 22, 1997


Frist family and Scully fund university projects
Gifts earmarked for a new campus center and a new dorm

Several alumni dug deep into their pockets to make major gifts to the university in September. The Frist family of Nashville, Tennessee, has committed $25 million over the next five years toward the construction of a new campus landmark: a multipurpose center with academic, dining, and recreational facilities, to be designed by architect Robert Venturi '47 *50. The new center will be called the Frist Campus Center. The other major gift, an undisclosed amount from John Scully '66, will go toward the construction of a new dormitory complex, to be located near the southern perimeter of the main campus, at the edge of the intramural playing fields.
The Frist family has extensive ties to the university, including U.S. Senator Bill Frist '74 of Tennessee, who is a charter trustee, and his brother Thomas Frist, Jr., M.D., whose sons Thomas III and William are members of the classes of 1991 and 1993, respectively.
To create the new center, the architectural firm of Venturi, Scott Brown and Associates will renovate and expand Palmer Hall, built in 1908 to house the physics department. Adding a four-story façade composed entirely of windows to the south end of Palmer will complete the "U" of the existing building, providing for easy circulation throughout the floors of the new center and ensuring the flow of natural light into high, open common spaces.
The new design maintains the integrity of Palmer's brick-and-limestone front façade, yet transforms the building's interior space with a four-level plan of meeting rooms and lounges, libraries and classrooms, and offices for student organizations. Also included in the new center will be a state-of-the-art facility with advanced teaching and learning technology, a dining area, a small theater, a café, and a reading room. The centerpiece of the Venturi design is a commons area, where students will come to pick up mail, rent videos, use cash machines, check their e-mail, and buy newspapers and magazines.
Venturi's firm, based in Philadelphia, has designed several other major buildings on campus, including Lewis Thomas Lab, Fisher Hall, and Wu Hall.
The members of the Frist family who contributed to the campus center include Bill Frist and his wife, Karyn, Tom Frist, Jr., and his wife, Patricia, and their sons Thomas and William. Senator Frist, elected to the Senate in 1994, is also a leading heart-and-lung-transplant surgeon. Tom Frist, Jr., was recently elected chairman and CEO of Columbia/HCA, the world's largest health-care company.

NEW DORMITORY
Designed by Rodolfo Machado of Machado and Silvetti of Boston, the new dorm complex will be named the Vincent and Celia Scully Dormitory, in honor of Scully's parents.
Scully is managing director of SPO Partners and Company, a private investment firm in Mill Valley, California. A founding board member of the Princeton University Investment Company, which manages the university's investments, Scully established a professorship in finance at Princeton in 1992 and is now a member of the trustees.
The design of the new three-and-a-half story complex, scheduled for completion in the fall of 1998, suggests the characteristic windows and towers of Princeton's Gothic buildings but also integrates the modern lines of the university's newest dormitories. The complex, which will include approximately 80,000 square feet, will have wings that form three sides of a quadrangle surrounding a central courtyard. The existing 1922 Hall, just west of the court, establishes the remaining side of the quadrangle. The wings will have three interconnected sections, each with its own kitchen, laundry, and study rooms. A highlight is the south wing, which will feature a wide archway topped by a modernized Gothic tower.
The Frist and Scully commitments are part of the five-year, $750 million Anniversary Campaign for Princeton. The campaign has raised some $456 million since it was launched in 1995. Princeton will continue to seek support to complete funding of the campus center and the new dorm.

A Nobel laureate's passion for fruit flies
"That should do it," says Eric F. Wieschaus, the Squibb Professor of Molecular Biology and a cowinner of the 1995 Nobel Prize in Physiology or Medicine. He has just finished fastening the tube-like lens of a movie camera into the shaft of a microscope. After focusing, he turns a knob on the camera, and the image of a fruit fly egg fills an adjacent TV screen.
This single-celled fertilized egg, or zygote, will develop into an adult fly of impressive structural complexity, a creature with a head, thorax, and abdomen, and bristling with legs, wings, and antennae. Wieschaus studies how flies--and by extension, more advanced animals, including humans--manage to perform this commonplace miracle of nature.
Next, he slips a videotape into a VCR and shows a time-lapse sequence of a fly going through gastrulation--"how your insides get inside you," as he puts it. On the TV screen, we watch a sheet of cells slide down the outside of an embryo and into an opening near its base. These cells will form the intestinal tract of the adult fly. Wieschaus smiles and says, "I got into this business because I found something that I liked. I saw these great things, and I knew I wanted to understand them."
Wieschaus grew up in Birmingham, Alabama, and he traces his passion for biology to a high-school science camp he attended at the University of Kansas in the summer of 1963. It was there that, through a microscope, he first watched an embryo go through a process known as cleavage, in which an egg develops a deepening furrow and divides into two hemispheres. More than 30 years later, his eyes still widen when he describes it. Although he had thought of becoming an artist, he traded his paints for biological stains at the University of Notre Dame, and went on to earn a doctorate at Yale.

HOW TO MAKE A FLY
The fruit fly (Drosophila melanogaster) has been one of the workhorses of genetics since early in this century. And gene splicing and related techniques developed in recent years have shown that a fly's genetic blueprint shares many similarities with a human's. In addition to what flies can tell us about our own genetics, they offer other advantages to laboratory scientists. Experiments can be conducted quickly because a fly develops from egg to embryo in 10 days, and generations turn over in just two weeks. Fruit flies are also easy and inexpensive to maintain: a single vial can hold hundreds of flies, which subsist on a gruel of cornmeal, yeast, and sugars.
A fruit fly's assembly instructions, like those of humans and all other organisms, are written in nature's alphabet of DNA--the letters A, C, G, and T, corresponding to four chemical compounds called nucleotides. A string of DNA, numbering anywhere from a few hundred to several thousand such letters, forms a gene. Fruit flies have about 20,000 genes (compared to some 65,000 in humans), each of which encodes a protein. Some proteins form cellular scaffolding, while others act as switches by activating, or expressing, other genes.
The expression of genes, especially during development, became the target of Wieschaus's work in the late 1970s at the European Molecular Biology Laboratory, in Heidelberg, Germany. By then, he says, "it was clear what genes were and how everything that an embryo does probably depends on gene products."
It was known that an embryo derived gene products from two sources--the (maternal-effect) genes of its mother and the (zygotic-effect) genes of the embryo itself. Maternal-effect genes act during the 10-day period required by the mother to make the egg. Zygotic genes become active after the egg is fertilized, during the brief 22 hours when the egg goes from a single-celled zygote to a 50,000-celled embryo.
Because the zygote develops so rapidly, Wieschaus and his laboratory partner, Christiane Nüsslein-Volhard, hypothesized that only a handful of gene products can be supplied by the embryo and that they must provide essential information about the localization of body structures. "When a particular cell--but not its neighbor--must have a particular product, then zygotic control is essential," Wieschaus explains.
Wieschaus and Nüsslein-Volhard (with whom he would later share the Nobel) set out to identify all the zygotic genes critical to development. They did this, essentially, by feeding flies mutagens--chemical substances that, by altering the sequence of nucleotides, either deactivate or overactivate certain genes--then observing what happened. If a gene was important to the orchestrated sequence of cell behaviors that occurs in development, deactivating it resulted in a mutation that either killed the embryo or left the fly with a physical abnormality.
By interbreeding flies, the two scientists established lines in which all members carried the same mutation. Ultimately they established some 40,000 lines, in which some 18,000 genes harbored mutations that affected a fly's survival. Using a microscope through which two people can look simultaneously, they sorted through flies they had fed mutagens, selecting out those that showed abnormalities in body axis or segment formation. In analyzing the mutant flies, they noted all sorts of unusual combinations of body parts. For example, one mutant, later named Krüppel, lacked all the segments of its thorax and the first five segments of its abdomen. Another mutant, even-skipped, contained half the normal number of thoracic and abdominal segments.
Overall, only 139 genes proved important in determining body structure and function. "We concluded that these 139 genes were the genes that controlled development in the fly," says Wieschaus. "By looking at these different mutant flies, we could gradually piece together the types of cellular decisions that an embryo makes during development." Wieschaus and Nüsslein-Volhard classified the genes responsible for the different malformations into three groups, according to the way they affect body segments and structure.
Despite the significance of their research, at the time few recognized its full impact. Explains Wieschaus, "It was only later that we learned that virtually all the genes we had identified exist in humans."
Because of continuing advances in laboratory techniques such as cloning and DNA sequencing, he adds, "the immediate applications of purely theoretical science have a much greater impact today." We now know, for example, that many aggressive human cancers result from the reactivation of developmental genes dormant since the first few weeks of life. Identifying these genes in fruit flies is a first step toward understanding how some cancers develop in humans and how their progression might be stopped.

STAYING FLEXIBLE
Despite his Nobel and the potential applications of his work toward curing cancer and other genetically based diseases, Wieschaus plays down any practical benefits of his research. "I did my work because it was interesting," he says. "Winning the Nobel Prize was never something that I had thought about or hoped for." Nor has it changed his attitude toward teaching or life in the laboratory. His recent undergraduate classes have included a freshman seminar on development and advanced courses on gene activation in embryos. Wieschaus's research team includes undergraduate thesis advisees, graduate students, and post-doctoral fellows.
Noting that the results of his experiments are usually different from what he expects, he says it's important to remain "flexible," and that often "the experiment shifts as it progresses." He adds, "Most of my experiments have failed in what we set out to do--but not in what we did." Whatever he discovers nurtures his curiosity to learn more, and always in a hands-on way. Like the time, as a teenager, when he first observed an embryo cleaving. "I want the visual impact myself," says Wieschaus. "It's not enough for me to run a lab and have other people get those experiences."
--Brian J. Wainger '97
Brian Wainger majored in molecular biology and is now a medical student at Columbia.

James Kraft '57's collection on display
This 1981 woodcut by American Richard Bosman, Man Overboard, is one of the works in the collection of James Kraft '57 on display through January 4 in the Art Museum. The exhibit showcases selections from Kraft's collection of prints, illustrated books, and photographs. The collection's strength is in contemporary prints, culled between 1975 and 1992, when Kraft gave his artwork to Princeton. Kraft's interest and taste in prints are broad--the works provide an overview of contemporary print-making during the last 20 years, principally in this country, although artists from other countries are included. Kraft collected prints by artists known predominantly for their painting and sculpture. Among those represented are Louisa Chase, Susan Crile, Eric Fischl, Sam Gilliam, Brice Marden, Elizabeth Murray, and David Salle. Kraft has worked principally in the not-for-profit sector as an administrator for such institutions as the National Endowment for the Humanities, the Whitney Museum of American Art, and the Manhattan School of Music.

In Brief
Oldest alumnus: Robert R. Lester '16, who was Princeton's oldest living alumnus, died at his home in Kansas City, Missouri, on September 11. He was 103. (See his memorial on page 47.) The oldest living alumnus now is Douglas R. Nichols '17, who is 103.

Rankings: Princeton placed first, tying with Harvard, in the annual college rankings published by U.S. News & World Report. The schools were followed in the rankings by Duke and Yale, which tied for third, Stanford, MIT, and Dartmouth and the University of Pennsylvania, which tied for seventh. Last year, Yale ranked first, Princeton second, and Harvard third. U.S. News ranked some 1,400 four-year colleges and universities. The rankings are based on the aggregate performances in seven categories. Princeton ranked first in alumni giving and with Stanford earned the highest score in academic reputation.

Beirut: John Waterbury '61, a professor of politics and international affairs, has been named president of the American University of Beirut, effective January 1, 1998. Waterbury will be the first on-site president of AUB since president Malcolm H. Kerr '53 was assassinated in 1984. Although AUB's administrative offices have been in New York City, the State Department recently revoked its ban on travel to Lebanon, and Waterbury plans to move to Beirut.

Prize: Charles C. Gillispie, a professor of history, emeritus, and professor of the history of science, emeritus, was awarded the 1997 Balzan Prize in the History and Philosophy of Science. He was cited for his "intellectually vigorous and exacting works." Gillispie, who joined the faculty in 1947, founded Princeton's history of science program in 1960.


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