Chemistry Professor Madeleine Joullié An Appreciation

“About ten years ago, Madeleine Joullié, G’50, Gr’53, was about to leave a clinic at Jefferson Hospital in Philadelphia following some medical tests.

“ You’ve got to see the doctor,” she was told. “You’ve got to wait.” Joullié braced for bad news. “ It’s an honor to meet you,” the physician, a woman, greeted her. “You probably don’t remember me.” “ No, I don’t, but probably I taught you Organic.” Joullié has been teaching Organic Chemistry in the School of Arts and Sciences (or its predecessor) since 1953, when she became an instructor. Later she would become the Ärst woman to join the department’s standing faculty.

“ I was a bio major,” the doctor reminded her. “I was scared to death of Organic. They told me there was this hysterical woman teaching the course. I came and talked to you, and then you encouraged me. You tutored me on Saturdays. You took me to ACS (American Chemical Society) meetings. You wanted me to be a chemist, but I wanted to be a doctor. You wrote me letters of recommendation. . . . I’m here because of you.”

For 50 years, future doctors, nurses, chemists, and other bright young minds have been taking Chem 241 and 242, or some earlier versions, from Joullié. In 1978, the ACS awarded her the Garvan Medal, in part for “devoted and inspirational teaching.” At the time, Chemical & Engineering News reported that Joullié was teaching more than 250 students each semester. “Every time I go to the hospital, there’s a good chance that I’ll run into someone I taught, but I don’t remember what grade I gave them.”

When the Nobel committee announced that alumnus Michael Brown, C’62, M’66, Hon’86, had won the 1985 prize for medicine, Joullié quickly called the College ofÄce. “Thank God,” she muttered when they told her Brown had received a good grade in Organic Chemistry. “I was worried I might have given him a C.”

At age 75, Joullié has intense blue eyes and close-cropped silver hair. One hand is black and blue and swollen from a recent fall. She still teaches, publishes scientiÄc papers (well over 200) at a rate of nearly one per month, and was recently elected District III director of ACS. An offer to edit a new chemistry journal had to be turned down. “She’s not just a venerable professor,” remarks chemistry professor Ralph Hirschmann, “ she’s a dynamo.”

Ask why she doesn’t retire and she replies, “because I don’t know how to do anything else. . . . I get up in the morning and I can’t wait to get to work. I’m annoyed at everything that gets in my way.” On her ofÄce door, graduate students have posted a sign that reads BOSS, which helps clarify the order of things on the fourth Åoor of the Chemistry building, in case there is any doubt. Photos of past students and their babies are scattered around her ofÄce.

Born in Paris, Joullié grew up within a protective family in Rio de Janeiro; she was not permitted to go downtown by herself. Hoping to expand his daughter’s horizons, her father shipped her off to Simmons College, a small women’s college
in Boston, where she took all the chemistry courses that were offered, earning a degree in three years. “I just loved being in the lab and making things,” she says. Many of her weekends were spent studying at the Boston Public Library, which maintained a set of Chemical Abstracts.

“ I remember one time on a Saturday,” she recounts, “some girl was crying in her room. I asked, ‘Why are you crying?’ I thought something was wrong with her.
She said, ‘Because I don’t have a date.’ I was pretty surprised that one would cry for something like that. It never occurred to me that I should have a date on Saturdays or any other day.”

Few of her classmates embarked upon careers at graduation: most went on to marriage. “I didn’t have a clear idea of what I would do,” she recalls. “But I didn’t feel comfortable with what I had learned, so I decided to go learn some more.” Her heroes were the likes of Louis Pasteur, Madame Curie, and Armauer Hansen, who discovered the leprosy bacillus. “I had the idea that I was going to cure diseases and save the world.” So, at the recommendation of “this guy” at MIT, Joullié came to Penn, where she was the only full-time female graduate student in chemistry.

In those days (1949), there were no bathrooms for women in the Harrison Chemical Laboratory, which housed the chemistry facility. Joullié had to cross an alley to the old Smith building, then known as the Hygiene building, where women technicians were at work on a government project. Many of the grad students were not reticent about reminding her of her place. “Girls don’t do well” in science, they told her. “At Ärst they tried to discourage me and make fun of me,” she remembers, “but when they realized that I was doing well, they wanted to copy my class notes.”

After earning a doctorate, she interviewed with DuPont but was told the chemical company only hired women in their library, not in their research divisions. She accepted a non-tenure-track position as an instructor at Penn, teaching undergraduate organic chemistry Äve days a week and running the lab. For Äve years, she had no graduate students and carried out research in collaboration with undergraduates. Later, only female grad students began to work with her. At faculty meetings the secretarial duties were usually delegated to her, and often the men would not take her comments seriously. “I got no respect, and,” she underscores, “I didn’t want any from people like that.”

In 1970, Joullié served on the Committee on the Status of Women, which collected and analyzed data to document the second-class standing of women on Penn’s faculty. The committee found that women constituted only seven percent of university faculty, fewer than six percent in the arts and sciences. “[That was] far fewer than would be expected by the number of women in the pool [of qualiÄed Ph.D.s],” remarks Helen Davies, Gr’60, a professor of microbiology in the medical school and fellow committee member. “The probability of that having been due to chance was . . . simply astronomical.” The report also found that women who held professorships were concentrated in the lowest ranks, received lower salaries, and waited longer for promotion than men. Joullié, an assistant professor at the time, was one of the “very, very few” women science professors on the arts-and-sciences faculty, Davies notes. The committee issued a number of recommendations that set the university on the path toward equal opportunity for women.

“ There were a few women in the early ‘70s who changed this institution,” observes chemistry professor Marsha Lester. “Madeleine was
one of them.” Lester is the second woman to join the ranks of the chemistry faculty. “Madeleine is very outspoken,” she comments. “She has an edge to her. . . . For a woman to have done this 30 years before I came—there had to be
an edge.” Adds Hirschmann, “Whenever she speaks at faculty meetings, there’s never any doubt about what she meant. It’s one of her charms.”

Later in the ‘70s, just before one of the regular faculty meetings, Vartan Gregorian, then SAS dean, put his arm around Joullié and pronounced, “Madeleine, I’m making you my afÄrmative action ofÄcer.” “ What is that?” she replied. “I’ve got to Änd out what it is, Ärst.” “ Never mind,” he explained, “we’re announcing it.”

Even though she was conscripted and was given no staff, Joullié didn’t wait to be told what to do but set the pace for change. Reviewing the NIH bluebook, which outlined afÄrmative action guidelines, she then met with department chairs —all men, she recalls pointedly—and explained how they would be required to make efforts to recruit women and minorities or else risk losing federal funding. From 1976 to 1980, she monitored the hiring and promotion of SAS faculty, comparing resumes of male and female candidates and sometimes refusing to sign off on hires that overlooked qualiÄed women. “Even though I was told that I was crazy, that I would cause faculty to resign, and that I didn’t know what I was doing,” she says, “I think I made the faculty aware of afÄrmative action.” Provost Eliot Stellar later appointed her chair of Penn’s Council for Equal Opportunity, which oversaw the activities of all schools’ afÄrmative action ofÄcers.

“ Madeleine was pivotal in this whole women’s movement at Penn,” says Davies. “One of the important things about her is that she is fearless and formidable. No matter what the cost to herself, if Madeleine feels that some information needs to be discussed—it may not be diplomatically correct at that moment—she will do it. She’s a brave human being and just plain honest.”

There is still some subtle and “hidden discrimination,” Joullié points out, but she believes women have made “tremendous progress” over the course of her career. “I used to say the best thing afÄrmative action did for women was to put a ladies’ room on every Åoor, which is true in a way. But it’s really done more than that. I think now, if they really want to, women can essentially do anything.”

In her Äeld of research, Joullié is a standout both as a woman and as a leading scientist, regardless of gender. “She’s one of the very few women—we can count them on two hands and maybe a foot— who do hardcore synthetic organic chemistry,” says Cynthia McClure, a young chemist from Montana State University who spent the fall in Joullié’s lab and in her home as a guest. McClure wanted to move into research on nitrogen-containing compounds, which are active
in biological systems like human bodies and thus key to making new drugs. “In order to be on the cutting edge,” she explains, “I needed to become better versed in the techniques and methods” the Penn chemist had pioneered for building customized and complex organic molecules. “She’s highly respected because her chemistry’s awesome and she publishes an amazing amount, and she develops new ways to make compounds—that’s what we all look for. . . . Her group is one of the leading laboratories in the world synthesizing bioactive nitrogenous compounds. Those of us in the Äeld regard her as the ‘Grande Dame’ of organic synthesis.”

Synthetic organic chemistry is the science of building designer molecules out of molecular pieces, sometimes with the aim of tweaking some basic molecular architecture to obtain a particular biomedical effect. Many of the synthesizing techniques are not yet at a stage where companies can enlist scientists to take up systematized or automated processes to create a desired product. The science is still very much an art form, and Joullié has excelled in pioneering methods that are simple, efÄcient, and elegant. Some of her syntheses are cited in the textbooks.

Calling herself a “pragmatic chemist,” Joullié has followed her intellectual curiosity, as well as the willingness of grant givers to provide funding, in deciding which projects to undertake. “If a problem involves chemistry,” she says, “I don’t care what the problem is, I will try to solve it.” Her research branches down a number of paths. Professor Barry Trost, C’62, a synthetic organic chemist at Stanford University and former student, points out that Joullié’s “seminal contributions” are in the synthesis of “very difÄcult classes of molecules of great importance because of their biological activity.”

One of those contributions involved collaboration with the renowned cancer warrior Judah Folkman at Harvard Medical School and National Medal of Science winner Paul Weisz, a professor (now emeritus) in Penn’s engineering school. For a long time, Folkman had been studying angiogenesis, the formation of new blood vessels, and its role in diseases that include tumor growth and some forms of blindness. Folkman had developed promising therapies that attacked angiogenesis, but there were problems with side effects. After reading one of Folkman’s papers, Weisz thought he saw a solution and sought out Joullié to design and piece together a molecular conÄguration that would work better. Together they synthesized beta-cyclodextrin sulfate, a sugar that attaches more effectively to the walls of growing blood vessels, delivering more of the steroid cortisone, which stops the growth of new capillaries. Subsequent tests showed that, with Joullié’s made-to-order compounds, Folkman’s original treatments could be made 100 to 1000 times more potent. Since webs of new blood vessels are vital to the growth and spread of malignant tumors, chemotherapies that target angiogenesis have become an important part of cancer-treatment regimens. Studies also indicate that beta-cyclodextrin sulfate reduces restenosis, the overproduction of cells on artery walls at the site of surgical procedures, growths that can lead to blockages. Joullié has also played a leading role in research on didemnins, natural products isolated from sea squirts. Didemnins are known to initiate apoptosis, or cell death, and thus have potent antitumor and immunosuppressive activities. She has produced several didemnin analogs, and she has synthesized probe molecules to track and study the biological activities of didemnins. One of the didemnin relatives she made, didemnin B, was reported to induce apoptosis more rapidly than any known compound. Newer, more potent versions are being synthesized in her lab.

Some of the substances Joullié has put together could previously be derived—with great effort and in small amounts—only from natural sources. Her syntheses have made available quantities of compounds that allow scientists to more thoroughly test and study their biomedical effects. Research she did on ninhydrins prompted a visit by Secret Service agents and led to Åuorescent products now used in some countries for Ängerprinting. “My experience is that nothing is trivial in chemistry,” she maintains, “but mostly we just have fun.” One of her current projects involves the synthesis of Isoroquefortine C, a substance found in the blue veins of Roquefort cheese.

Two years ago, Philadelphia Magazine named her one of the “ 76 smartest people in Philadelphia,” and she has a closet full of awards, culminating in the prestigious 2002 Cope Senior Scholar Award from the ACS. “Madeleine’s career is that of a woman pioneer,” notes Hirschmann, who is a member of the National Academy of Sciences and a National Medal of Science laureate. “She was the Ärst woman organic chemist to be appointed to a tenure track position in a major American University. She has a distinguished record as a scientist, as a teacher, and as a mentor of students regardless of sex, and she remains a highly active, highly productive, well-funded organic chemist.”

Looking back over her research achievements, Joullié muses ruefully, “We had big ambitions of doing things to make the world better, but I don’t think I’ve done anything great. I was pretty naïve, right?”

You can never tell. Over her half century at Penn, she has produced
a lot of basic research, yielding a rich body of knowledge whose future application is impossible to make out. “Sometimes things turn out [to be] more important than you think,” she considers. “In this business, it’s not always easy to predict.”

She’s right—not just about the vagaries of doing science but about the unforeseen futures that unfold from teaching. In 1998, the American Chemical Society honored Joullié for her contributions as a mentor and teacher with its Award for Encouraging Women into Careers in the Chemical Sciences.

As a graduate student in 1959, Helen Davies took Qualitative Organic Analysis with Joullié. “She was magniÄcent,” Davies recalls. “ I had never had a woman teacher at the University of Pennsylvania until I had Madeleine. . . . It made me aware that a women faculty member could exist, which was not always apparent then in most departments.” The sentiment echoes the undergraduate who long ago took Organic with Joullié and later examined her as a physician: “I’m here because of you.”

“ I think that’s true in so many, many cases,” surmises Davies, counting herself as one among that multitude. “It’s just the story of her life.”