Five Years Later

Three women chemists received MacArthur Fellowships in 1999. C&EN's Maureen Rouhi visited each of them at the time and captured the lives of these unique, innovative, and highly productive women: Laura L. Kiessling, a professor of chemistry and biochemistry at the University of Wisconsin, Madison (UWM); Wilma A. Subra, an environmental chemistry consultant in Louisiana; and Carolyn R. Bertozzi, professor of chemistry at the University of California, Berkeley (C&EN, Jan. 31, 2000, page 25).

By granting the five-year awards, the MacArthur Foundation was predicting that the women would continue to contribute and create in significant ways. They have.

C&EN recently visited all three women again at the end of their fellowships and found them still engrossed in the work that occupied them in 1999. Bertozzi and Kiessling continue to expand the frontiers of chemical biology. And Subra still advocates for communities affected by environmental issues.

The fellowship changed some things. It gave them some financial freedom. The award made them more visible and provided opportunities to speak to more people, especially outside their particular specialties. All of the women are charismatic and lucid speakers. They can take a hairy chemical concept, distill it to its essentials, and effectively relate it to a wide range of audiences. In addition, the award may have contributed to their confidence, encouraging them to range further and be more daring.

As a follow-up, C&EN recently shadowed each woman for a day. What follows are snapshots of their different daily tasks, thought processes, and motivations.

MARCH 25, 2004, 9:23 AM. "About 50% of the proteins in human cells are glycosylated," Laura Kiessling lectures in her course on chemical biology for graduate students at UWM. She pauses, walks toward the class, and says with amazement, "That's a lot!"

Kiessling sheds energy. She has the agility of a track star, and she wanders the full width and length of her lecture space as she talks. Her lecturing has a lighthearted, dramatic flair, and her love for the subject is contagious. She pauses for emphasis, enunciates, looks carefully at the crowd of students, and helps them imagine what she sees in her head.

"We are trying to teach chemists how to discover biology and tell biologists how to do chemistry." Kiessling team-teaches the class with her husband, Ron Raines, and their colleague Peter Belshaw, both of whom are professors of chemistry and biochemistry on the Madison campus. Graduate students from a variety of departments sign up for the course. Kiessling takes the task of teaching this kind of crossover seriously--one reason why she stayed up till 1 AM working on today's lecture. Scientists working at the junction of chemistry and biology, she believes, are making extremely important breakthroughs.

Glycosylation was one of Kiessling's first research loves. Her synthesis of multivalent glycopolymers that influence the availability of proteins on the surface of white blood cells led to her first Nature paper. Multivalency, white blood cell behavior (including chemotaxis), and the synthesis of ligands that influence cellular receptors are all still current arms of her research. But her research has grown additional thrusts as well. She's dipping into stem cell differentiation, the circadian rhythms of the worm Caenorhabditis elegans, and how enzymes construct the cell wall of Mycobacterium tuberculosis. And she has no qualms about trying out a new technique or procedure to answer a question--whether it be organic synthesis, protein crystallography, or phage display.

That's the thing. Kiessling really can't be pinned down. She is constantly ranging further afield, way past her own and her students' comfort zones.

Kiessling has always been that way. But she admits that receiving the MacArthur fellowship has encouraged her penchant for entering new fields. "If you move into new areas," something Kiessling seems almost addicted to, "you are always at a point where maybe people can find fault with you. It's risky." Receiving the fellowship, she says, gave her more confidence and incentive to move into new areas. In addition, she says, now people give her the benefit of the doubt that she will succeed there, especially in new communities that don't know her yet. Just this summer, Kiessling was invited to speak at three separate Gordon Conferences--each with a different focus.

Five years ago, C&EN noted that Kiessling's movement into new fields is motivated by her ability to see new connections between systems that seem to have nothing to do with each other. Her ideas have helped bring about new ways of thinking about biological mechanisms and pathways. For example, instead of the idea that one receptor belongs to one binding site, Kiessling has shown that the body often works in clusters of receptors that bind to multiple binding sites. Or she might see that the same type of receptor clustering important in chemotaxis is important in stem cell differentiation.

"She's like a spider," says Ratmir Derda, a third-year graduate student in Kiessling's laboratory. "More than building foundations, she builds bridges between fields. Her new connections create a rich web," he says.

Kiessling is currently highly invested in helping students and those new to the field to see the connections that she sees. She chaired the National Institutes of Health Bioorganic & Natural Products Study Section because she wants to give young people chances to pursue ideas in areas that are new to them. She heads UWM's chemical biology interface graduate training program, which provides fellowships for incoming graduate students interested in chemical biology research. She has spearheaded a cluster hire of new faculty at UWM. All of the new hires have an interest in chemical biology work, but they aren't necessarily hired into the same department.

In her own laboratory, she accepts students from diverse backgrounds and then gives them a great deal of freedom. "Through this amalgamation, this fermentation of varied people, new things come about," says Brendan Orner, a postdoc in the lab. "Then after we go into the desert and do some crazy research, we have to come back and account for it."

10:57 AM. Kiessling rummages in her bag for her car keys so she can drive from the biochemistry building to the chemistry building. Kiessling often shuttles between the two because she has a lab and an office in each, as well as two groups of graduate students. "Losing keys is one of my major talents. I'm working on cultivating the 'confused professor' stereotype--one who is thinking about more important things," she says wryly and laughs.

In truth, she probably is. She's probably thinking about a conversation she wants to have with a graduate student or a collaborator. In fact, Kiessling just might go ahead and start the dialogue in her head. "Our running joke," says Michelle Soltero-Higgin, who just graduated from Kiessling's lab, "is that she has an ongoing conversation in her head, and when she opens her mouth, it just starts mid-sentence. Her brain is going a mile a minute."

Kiessling ticks off the people she's been meaning to talk to. "There are a couple of conversations I want to have. I want to talk to Dave about where he is, because I know he was working up the data for his circadian rhythms experiment. I want to talk to Brendan about what proteins we are going to put down on these surfaces. And I just talked to Grace because she just finished her seminar requirements, so I want to get her back up and running in the lab. Every day, there are a couple of people I am thinking, 'OK, I need to talk to them.'"

Having interesting scientific conversations is crucial to Kiessling's work and thinking processes. It is often how she comes up with ideas. It helps her turn nascent ideas into projects, papers, and even programs. She'll chat in the laboratory with graduate students, on the phone with colleagues, over dinner with Raines, and at meetings and other forums such as NIH study sections. "Those conversations are also good to have on the weekends, when I have a little more time. The worst is to have an interesting conversation and then have to run off."

Sometimes, Kiessling has to break off conversation so that she can pick up her daughter Kyra, now five years old, from kindergarten. (She and Raines trade off picking her up.) Kiessling and Raines are aware of the challenges of raising a child while leading active research groups, teaching, and maintaining full travel schedules. Receiving the MacArthur fellowship actually made it easier. Kiessling was able to use some of the fellowship money to bring Kyra and childcare along with her when she traveled to research conferences or to speaking engagements.

Nevertheless, the couple's time is more ordered because of Kyra. Almost always, they eat breakfast and dinner together. Kiessling and Raines alternate staying late at work. And Kiessling avoids attending meetings or committees that meet on the weekends. Kiessling does often go into the office on weekends, yet she will try to keep it to either Saturday or Sunday. Less interrupted weekend time is precious, she says. Writing, editing, and some important conversations tend to happen then.

Kiessling believes she hasn't had to compromise time with Kyra for her career or vice versa. "Everything in life is an orienting of priorities. And everybody has to do that whether you have kids or not. I still do so much. I am a better mom because I am happy when I am doing my work. I would not be as happy if I felt like I was constantly making huge compromises."

Kiessling is working to make the path easier for other women who follow her. Raines and Kiessling are trying to set up a small grant program at UWM for graduate students who are expecting children. They are lobbying organizations like the American Chemical Society to provide daycare at meetings. (At one of the Gordon Conferences that Kiessling and Raines attended this summer, the organizers helped arrange for daycare. Kyra was even allowed to put up a special poster at the poster session.) Kiessling has also tried to create a place in the schools' buildings for nursing mothers. She wants to give the kind of support to both women and men in science that she herself feels--so they feel comfortable aspiring to tasks that may seem difficult at first.

"I think that sometimes people do not shoot high enough. They are afraid that they might fail, or they might find themselves in a situation where their life does not have the right balance or where they are unhappy. I would say that I am not afraid to fail. I hope to instill that in my daughter as well. I think that we always have a chance to adjust our lives, our ambitions, our aspirations downward. It is always worth pushing yourself to see what you can do. I think that most of us will be surprised at what is possible."

APRIL 19, 2004, 8:37 AM. On a two-lane road leading to Baton Rouge, Wilma Subra describes the land outside her window. She points out a stretch of antebellum homes and yards displaying 100-year-old oak trees dripping with moss. Along a raised section of road, she talks about the Atchafalaya Swamp, "the largest overflow swamp in the U.S.," with islands of twist-rooted cypress trees.

Subra also slips into describing what is inside the soil--the underside of Louisiana with its confluence of aquifers, oil wells, and waste sites. "There is drilling and production in every parish in the state of Louisiana," she says. Pipelines, industrial facilities, wells, old hazardous waste sites, and solid waste sites "are sprinkled like salt and pepper all over the state. That is the state of Louisiana. It is a mass of waste sites that contaminate the air, contaminate the soil, contaminate the water."

Subra is in no way vitriolic. Rather, this woman in comfortable shoes is matter-of-fact. For over a quarter-century, in between her work as an analytical chemist and her caring for children and grandchildren, Subra has volunteered her time as a technical consultant for 500 to 600 communities impacted by environmental contamination.

Although much of what Subra does results in a cleaner environment, "activist" is the wrong description for her--"fact distributor" is better. She tells community members how to find information about what is being released, where it is being released from, what health effects it might have, and what legal recourse they might have for reducing it.

She says the MacArthur award "has enabled me to never tell anyone 'No.'" When a group or individual calls her up for help, she can advise them regardless of whether or not they can pay for her services. (Her husband, Clint Subra, estimates that Subra donates 60 to 70% of her time--often to low-income communities at company fence lines.) The fellowship also greatly expanded Subra's reach. It gave her the financial support to travel and speak more and enhanced her profile. She regularly gets calls from communities, government committees, and individuals across the country.

Naturally, she has continued her work where she started: in Louisiana. She has worked in Vermillion Parish since the mid-1970s, when she helped get the 55 oil-field waste sites within its borders shut down and covered over with dirt.

In 2001, a new company proposed opening a new waste-oil recycling site in the area, and the community members balked. They called Subra. The police jury and the school board issued resolutions opposing the request. More than 200 citizens, including elementary school children with banners, showed up at the public hearing for the Louisiana Office of Conservation to express their opposition.

When Subra got up to speak, she described in detail how the permit application was deficient according to state law and did not promise that the proper safeguards would be in place to keep the waste from affecting the community, especially one already burdened with so much oil-field waste. The crowd gave her a standing ovation. Ten months later, the company withdrew its application.

Subra has spent decades culling from government reports, databases, and public documents what is relevant and important for the community. She searches the Toxics Release Inventory maintained by the Environmental Protection Agency, requests accidental release reports from local emergency planning commissions, and goes to bed at night reading permit applications.

Her chemistry background--a B.S. and an M.S. in both chemistry and microbiology from the University of Southwestern Louisiana--helps, but Subra is also simply good with facts. "She's like an elephant," Clint Subra says. "She never forgets. If you pick her brain, she can tell you the courses she took in college, when she took them, what she learned in that course, who the teacher was, what year she took it, and what grade she made. Well, you know she had an A. She made an A in everything." That talent allows Subra to repeat particularly relevant facts at especially relevant times. "I'm just telling them what they already know--or should know," she says. "They reported the data."

By "they," Subra is referring to companies--the oil companies, chemical manufacturers, or power plants that she is often at odds with. Subra isn't out to shut those firms down. The companies generally provide livelihoods for the communities she helps. She wants to find workable solutions so that the firms can operate without harming their communities.

"You are really educating [the companies]," Subra says, "on what their self-reported data say. You just have to keep at it because, sooner or later, it is going to finally get through to them that it matters. And then they are going to use the data that you provided to make really beneficial decisions for the community."

And that, according to Helen Vinton at Southern Mutual Help Association, is what sets Subra apart. "You can find the rabble-rousers. But to be able to say why there is a problem, talk to both sides, and solve it--that has been the jewel of her work. There has been real improvement."

It's slow. A great deal of Subra's work consists of going from one community to another, each with different contaminants from different sources. Often a change that she helps effect in one area doesn't apply to another area. Communities in Louisiana affected by oil-field waste have to turn to local or state bodies for regulation because oil-field waste is exempt from regulation at the federal level.

Yet she has begun to see change. Once enough individual communities encounter the same problem, some coalitions--for example, the Louisiana Environmental Action Network--work to enact changes regionally. Subra consults for them, too. Increasingly, Subra is being invited to serve on national and state committees as a grassroots representative. Currently, she is on four EPA committees and also serves on the National Environmental Justice Advisory Council, which advises the administrator of EPA on serving the needs of minority and low-income communities. "We're getting there little by little by little," she says. "When the community is educated, they can be the eyes and ears."

Subra is a familiar figure at EPA and the Louisiana State Courthouse. She is famous at universities. And she is almost deified in the buzz that flows from one community she has helped to another. Yet Subra rarely talks about what she does, and at home, she blends into the crowd.

Her husband, a friendly medical technologist who works in the laboratory at the local hospital, is much more well known in their own community. "I hate going to Wal-Mart with him," she remarks. "He has taken the blood of everyone in town."

Subra used to have an assistant but now works alone out of the three-room office of Subra Co., e-mailing, consulting, traveling, participating on panels, and driving to the Louisiana Senate offices. The office--improved from a trailer five years ago--holds a typewriter, a computer, a refrigerator, a fax machine, a copy machine, bookcases and boxes packed from years of document gathering, and a small laboratory. She still keeps up her analytical chemistry work, testing pickles and hot sauce from the local factory for bacteria, or preparing a nutritional label for the lady who sells her crawfish cakes at the town diner.

Every once in a while, Subra goes across the street to check up on her neighbor, whose husband recently passed away. Every Monday, she takes her granddaughter Celine to dance. Time with her grandchildren--three of them now--is her most treasured time. When she is with them, she says, "the world stops for that half hour. You sit on the floor, and you play with them. It doesn't matter how many projects you have to go do, or how many reports, or whether you have prepared a presentation--at the time they are here, you tend to them."

Subra's own community has its environmental issues, and Subra helps where she sees a need. Most of the land around her town of New Iberia grows sugarcane. From about September to January, a good portion of the neighborhood works farmer hours--12-hour days for the harvesting of the sugarcane. It is difficult to get all of the fibrous cane off the fields without burning it off, and one of the signs of sugarcane harvest time is the sight of burning fields.

"For one-third of the year, you can see a haze of sugarcane smoke," Subra says. She and others believe this widespread burning leads to a host of respiratory ailments in the communities surrounding the cane fields. Subra heads the local emergency planning commission, and she'll get calls, especially from parents, on bad smoke days.

When she gets a call that smoke is blowing into a school, she calls the local authorities. And she keeps a record of complaints that she hears. If the community decides to try to get legislation enacted, she'll have some facts at hand.

The sugarcane issue has two sides for everyone in New Iberia, including Subra. Her youngest daughter married a sugarcane farmer. Troy Freyou and his father own about 2,000 acres of the hardy crop, and they are dependent on the success of each year's harvest.

"I get a lot of flak" from the other farmers for Subra's involvement, Freyou says. "They ask me what my mother-in-law is doing." But Freyou and Subra respect one another, and Subra has never been one to avoid complexity. She will continue to work at finding a solution that allows the community to both make a living and live without the contamination that could harm it.

APRIL 6, 2004, 6:14 AM. In the gray light of dawn, Carolyn Bertozzi bikes into the foothills above the University of California, Berkeley. On clear days, as the sun comes up, she can see across San Francisco Bay to downtown San Francisco and past that to the sea. Biking is a new outlet for Bertozzi. Running has always been her favorite workout. But after Bertozzi hurt her foot trying out tennis, her partner gave her a mountain bike.

Bertozzi would never claim to be a morning person. The UC Berkeley professor with a joint appointment in biology and chemistry generally makes it to work a few moments before her first meeting of the day and grabs a muffin for breakfast.

But her early-morning biking routine is characteristic of how Bertozzi approaches everything. She will put in an extraordinary amount of effort to do something well, especially when first learning it. Her demeanor is often nonchalant. She looks almost like a casual undergraduate student in a leather jacket and jeans, holding a bottle of root beer. But Bertozzi is a Howard Hughes Fellow, recipient of the MacArthur award, sought-after speaker, cofounder of a start-up company, and principal investigator of a 35-person chemical biology laboratory.

"Considering the amount of energy she expends on a daily basis, you'd think she would flame out," says Chris de Graffenried, a new Ph.D. who just graduated from the Bertozzi lab.

Five years ago, C&EN described Bertozzi as an enthusiastic, risk-taking young investigator three years into leading a laboratory. In many ways, the primary difference today is that she is simply juggling more responsibilities.

Bertozzi now cochairs the chemical biology graduate program that she started in 2000. She has a faculty appointment at UC San Francisco in molecular pharmacology. In 2001, she helped start a company called Thios Pharmaceuticals. Thios means sulfur in Greek, and the small drug discovery firm specializes in sulfation pathways.

But besides spreading herself more thinly, Bertozzi has become more experienced, and her laboratory has ripened. "We were a pretty young lab" five years ago, Bertozzi recollects. "I hadn't graduated any students at that point." She had not yet made tenure, and most of the group projects were those that Bertozzi had come ready to start her own lab with.

Now 20 theses sit on the shelf. Her laboratory has greater resources, her projects are more mature, and students come and go in roughly the same ratio. Bertozzi describes her lab now as one at equilibrium.

Not that Bertozzi herself isn't changing. In fact, she says she has learned how important it is to regularly reinvent oneself. Five years ago, Bertozzi entered what was for her the brand new field of tuberculosis research. Now, she is foraying into materials science and nanotechnology. She has joined a group of UC Berkeley professors and Lawrence Berkeley National Laboratory scientists to start up the Molecular Foundry, a place where new materials at the nanoscale are formed. At the foundry, techniques of traditional synthetic chemistry, materials science, and biology are available for researchers to create new molecules and materials. Bertozzi's group is especially interested in the synthesis of inorganic/organic composites that mimic biological materials such as bone.

Bertozzi credits her students with pushing her in entirely new directions. "It is easy to talk yourself out of pursuing new directions when you are deeply entrenched in a certain area of research. There are also funding limitations that might prohibit you from taking such risks. But new students are not limited by such thoughts and are therefore willing to take risks. They will take you in directions that you might never have embarked on as a senior person with an established research portfolio. I have learned to take a leap of faith and follow the interests and instincts of the students."

8:18 PM.Bertozzi wanders out of her office holding a tennis ball, trying to think. She absentmindedly dribbles the ball, flings it to the wall, and catches it again. She paces and dribbles and talks to herself and the three graduate students who pass by, working out in her mind the best way to describe her research.

Movement has something to do with how Bertozzi thinks. "Sometimes, if I'm working on a grant, I'm out there procrastinating: yo-yos, tennis ball, anything to get the words out." Her office closet contains a tennis racket, a Slinky, a stress ball, a soccer ball, and a yo-yo. Perhaps it is the pianist in her--she creates best when using her hands.

"She's always tinkering," postdoc Penny Drake says. "If there are things out in front of her in a physical way, she always has her hands on them, moving them around."

In the evening, especially, Bertozzi pulls out her toys. From 7 PM to midnight, Bertozzi says, is her best time, when "I am most accessible, most creative, most thoughtful." A lot of editing and drafting is done in the evening hours and on weekends. A lot of brainstorming is done then, too.

She often prepares lectures in the evening. Bertozzi is a gifted and lucid speaker with an ability to tell a simple, engaging story. "It's amazing to see her take this complex topic and distill it down to something my mother could understand," says Jennifer Prescher, a fourth-year graduate student in Bertozzi's lab.

The MacArthur fellowship only increased the demand for her as a speaker. A number of months this year, Bertozzi was in town only about half the time.

The regular travel and the long days and weeks at the university can sometimes take their toll. It's intense, she admits. Yet "when you are in it, you just do it and have fun. It goes in cycles. There are times when I am driving myself day in and out for months on end. And there are other times when I'm kind of tired. I go to Hawaii for a week in the summer."

This past year has been one of the months-on-end years. "It seems like every year gets more busy," she says. "What gives is that I'm not at home as much," Bertozzi adds quietly. "This semester has been particularly bad." She and her partner, Cynthia Williams, have a home near the university, which they bought when Williams was in school to become a nurse practitioner. Without the MacArthur award, Bertozzi says, they never could have afforded a home near Berkeley. Williams is now working as a practitioner at Planned Parenthood in Hayward. She has a 45-minute commute, which, combined with Bertozzi's schedule, means they spend even less time together every day.

For her students, Bertozzi's drive is inspiring. They admire the depths of energy she seems to pull from, and they are grateful for the hours she spends in the office on their behalf. At the same time, graduate student Nick Aagard says, "Maybe she gives up too much--what would be too much for me--to get what she wants."

Bertozzi is aware of the no-kids, workaholic stereotype that seems to fit her life. She understands that others wouldn't choose to spend their time so intensely involved in their vocation. "But I don't feel that I have sacrificed. I imagine there are other dimensions I still might add to my life. I would just work them in somehow--like, for example, having children." If Williams and Bertozzi were to raise a child, she says, she would figure it out and change her schedule accordingly.

Bertozzi tells her students that they can certainly create a life that includes dinner at home in the evening and some weekend trips. "Life is all about making choices, and sacrificing some things for other things. Even within my job, I sacrifice some things for other things. Prioritization and decision-making are a major part of the job."

What keeps her going, she says, is "the challenge of deconvoluting these complex biological systems and understanding them at the chemical level." Plus, Bertozzi feels the weight of being in a unique position. There are few female organic chemists, and Bertozzi wants to do the best job she can so that she can pave a way for others. And maybe more motivating than all the rest--at least on a daily level--is that "I want my students to be successful. I try to focus on the challenges they are about to face and prepare them as best as I can, irrespective of the time of day or hours it may require."

It's kind of like being a parent, she says. Bertozzi actually regularly jokes about being a mother to her students. She talks about her pride in them, in "having my own scientific offspring out in the world." She talks about how she worries about them and feels separation anxiety as they prepare to leave.

The feeling has intensified over the years. "I am ever more aware that eventually all of my students and postdocs will move on to the next stage of their careers. I have a few precious years during which we can work together directly, and I want to enjoy every minute. I don't think I appreciated before what a privilege it would be to get to know them." She tells graduate student Sarah Luchansky not to go, and Luchansky smiles like a teenager humoring a parent who worries. "It's a rotating door for them," Bertozzi says with a wistful grin. "But I'm always here."