MEDICINE

What Stem Cells Teach Us About Cancer, and Vice Versa

TO WATCH IRVING WEISSMAN draw pictures of red blood cells and T lymphocytes on his office whiteboard is to catch a glimpse of the investigative passions that fuel his research. After filling the board with dashed-off circles and lots of linking lines, the professor of cancer biology tap-tap-taps on the ultimate object of his diagram—a solitary, blood-forming stem cell. “It’s the only cell that self-renews, so it obviously must know which genes to turn on, to make more blood cells,” he says.

Stem cells’ self-renewing property is both good news and bad news for people with cancer. The good news: at least in the blood-forming system, adult stem cells can be used to regenerate cells destroyed by radiation and chemotherapy. In a patient with metastatic breast cancer, for instance, “in order to get to the dose that kills all the cancer cells, you’ve killed all the blood-forming cells,” explains Weissman, MD ’65. “In 40 percent of cases, the bone marrow has breast cancer cells in it, so [if you do a transplant using the patient’s own marrow], you’re going to redeliver the breast cancer to the patient.” In the mid-’90s, Weissman and colleagues demonstrated that giving breast- and blood-cancer patients only blood-forming stem cells regenerates marrow without the risk of reintroducing cancer.

The bad news: cancer has its own stem cells, according to breast-cancer studies at the University of Michigan and Weissman’s research on mice with leukemia. “The cell that’s really important for the cancer, the one that spreads the cancer from one part of the body to the other, is a cancer stem cell,” he says. But even bad news may lead to better treatment: Weissman hopes he and others can identify the genes that allow cancer stem cells to self-renew, then develop drugs that target those cells.

At Stanford’s new Institute for Cancer/ Stem Cell Biology and Medicine, Weissman wants to bring together researchers and clinicians who will investigate adult stem-cell therapies and methods to combat cancer stem cells for many types of malignancies. A leading figure in adult stem-cell research, Weissman will direct the $120 million institute, which received $12 million in seed money from an anonymous donor in December.

Eventually, Weissman also wants the institute to create new human pluripotent, or embryonic, stem-cell lines. While adult stem cells may only be able to create one type of tissue—blood stem cells form blood, muscle stem cells form muscle tissue and so on—pluripotent stem cells can generate any type. Weissman wants researchers at the institute to be able to study pluripotent stem cells that carry mutations found in cancer and in other genetic diseases, including Parkinson’s and Alzheimer’s.

In August 2001, President Bush restricted federal funding for embryonic stem-cell research to projects using existing cell lines, none of which carry such mutations. To create the mutation-carrying lines, researchers may use a lab technique called nuclear transplantation: removing an egg’s nucleus and replacing it with an adult nucleus, then, after the cell has divided and formed a ball of cells called a blastocyst, removing the stem cells.

This process is controversial. Removing the stem cells destroys the blastocyst, which some consider a human life. Others are concerned because nuclear transplantation employs the same steps as human reproductive cloning, except for the ultimate implantation in a woman’s uterus. Weissman sees a clear distinction between the two. “I was chair of the National Academies committee that called for a legally enforceable ban on human reproductive cloning because it was so dangerous,” he says.

Nuclear transplantation is the subject of competing U.S. Senate bills and White House criticism. Weissman hopes the federal government will follow California’s lead and allow it. “If the President is objective and serious about human diseases,” he says, “he’ll look at all of the new data before he makes his final decision.”

TECHNOLOGY

Make New Friends—Link to the Old

THEY SAY IT'S ALL ABOUT who you know. But for Orkut Buyukkokten and Tyler Ziemann, it’s actually about who you don’t know. As a doctoral student in computer science, Buyukkokten noticed that his fellow graduate students had a hard time meeting people with similar interests. In November 2001, he came up with the idea of an online social networking forum.

Buyukkokten, PhD ’02, recruited Ziemann, ’02, a political science major, to manage the creative and business aspects of the project. Together they created Club Nexus, a free service exclusively for Stanford students.

Club Nexus users introduce themselves by filling out profiles that can contain anything and everything from which dorm they live in to their sexual habits. They then link themselves to students they already know, and voilà! A user wants to find out who her friends’ friends are? She can view a graphical representation of the connections between Club Nexus’s members, with herself at the center. She’s dying to find out who knows someone who knows someone who knows the cute guy in Spanish class? The “shortest path” feature—a.k.a. the six degrees of separation concept—will tell her. She’s looking for a running partner who lives in Wilbur? She can apply a couple of filters and find candidates.

“The core idea of it is really useful,” says Ryan Barrett, ’02, a coterminal master’s student in computer science. “It gives you a good context to know who someone is when you know who their group of friends is.”

Club Nexus also has bells and whistles. Forums provide opportunities to discuss politics or class reading, though the two most popular focus on remedying the supposed lack of sexual activity at Stanford. In the Karma Network, students rank each other based on niceness, trustworthiness, coolness and sexiness. The algorithm worked (as measured by the third-place finish of the masterminds’ test subject, a popular student named Caroline), but received criticism from students expecting higher marks for themselves.

“Some people were upset because they’re not sexy,” says Buyokkokten.

The network initiated to connect graduate students has become widely used—by undergrads, who account for 80 percent of the 2,383 participants. “It is successful because we could do this in a closed, trusted community,” Ziemann says. “Anywhere else, you wouldn’t post this information.”

Through their new company, Affinity Engines, Ziemann and Buyokkokten hope to market the concept to other communities. Their first client: the Stanford Alumni Association, which rolled out a network called inCircle in January. Discussions are expected to be less risqué than in the student version, and to include professional networking. But the product is no less popular: 3 1/2 weeks after launch, 10,652 alumni had logged in.

So how did a computer science doctoral student and a political science undergrad meet in the first place? Through a friend of a friend, of course.

For more: clubnexus.stanford.edu, incircle.stanfordalumni.org

Cardinal Numbers

Coldest temperature, in Fahrenheit, ever recorded in Antarctica: –129

Approximate increase, in feet, of worldwide sea level if Antarctica melted: 200

Percent of U.S. population displaced if sea level rose 30 feet: 26

Antarctic research scientists, including Stanford professor Rob Dunbar, aboard the icebreaker Nathaniel B. Palmer during its January 2001 voyage: 25

Female scientists aboard the Palmer: 17

Top waddle speed, in miles per hour, of Antarctica’s emperor penguin: 1.7

Sources: Stanford department of geological and environmental sciences; Environmental News Network; Sea World Adventure Parks

RESEARCH

The Origin of Species

THE INCH-LONG FISH in the laboratory vial wouldn’t catch any angler’s eye, not even as bait. A second specimen, although double in size, is equally unremarkable.

“If you plunked these two fish down in front of most people, they wouldn’t recognize them as the same species,” says David Kingsley, an associate investigator of the Howard Hughes Medical Institute and associate professor of developmental biology at Stanford.

But the fact that the two fish are far-flung cousins—one was trapped near Canada’s Queen Charlotte Islands, the other was taken from Scottish seas—makes Kingsley one happy researcher. The cold-water aquariums in his lab hold specimens from more than 30 locations around the world, and he is cross-breeding thousands of the unassuming little fish with the great big name: three-spine stickleback.

Scientists know that populations of sticklebacks were isolated from one another some 10,000 years ago, when melting glaciers dispersed them into tens of thousands of different lakes and streams. Generations of biologists have identified the dramatic differences that distinguish today’s sticklebacks, including body size, color, skeletal armor, fins and behavior. Now Kingsley is using the tools of molecular genetics and genomics in an effort to find the bases of those differences—in essence, identifying the genes that control the evolution of new traits in vertebrates.

If Kingsley dotes on sticklebacks, associate professor of developmental biology William Talbot, PhD ’93, is just as jazzed about zebra fish. In his tropical-temperature lab, Talbot is raising more than 15,000 blue, silver, yellow and variously striped zebras. After a gene or gene family is tentatively identified—in zebra fish or, sometimes, other vertebrates—Talbot tests its function by disabling it in zebra fish. Because zebra fish reproduce quickly and copiously, the genes’ roles soon become apparent.

Kingsley and Talbot, along with Richard Myers, chair of genetics and director of the Human Genome Center, have made such a splash with their research that they recently landed a five-year, $16 million Center of Excellence in Genomic Science grant from the National Human Genome Research Institute.

With their respective knowledge of sticklebacks, zebra fish and genomics, “we each bring something totally different to the table,” Myers says. “Some questions are better asked in one species,” adds Talbot. “If we need to knock out 100 genes, we would do that in the zebra fish, at least first. But a key part of the grant is understanding the natural variation that leads to differences, which is something we can’t address anywhere but [in the] stickleback.”

“These guys are trying to answer some fundamental questions about how species occur,” Myers says. “When we started the genome project, everybody knew, even strict human geneticists, that we were going to learn far more by studying organisms that we could manipulate and do experiments with.”

FACILITIES

Not Easy Being Green? Check Out Jasper Ridge

AT FIRST, his office was a 1979 Dodge pickup. Then, a used 1992 Isuzu Trooper with four-wheel drive. Sure, he had an office on campus, but when the administrative director of the Jasper Ridge Biological Preserve needed to work on-site, his car became his work space, holding his files and notes. There was a small trailer on the preserve, but space was so limited inside that research material had to be kept in a nearby shed.

By the late 1990s, director Philippe Cohen was lobbying for an all-encompassing building serving the needs of researchers, students and administrators—but it had to be built right. It had to fit with the Stanford preserve’s mission: to contribute to the understanding of the Earth’s systems and protect natural resources.

Accordingly, Jasper Ridge’s 10,000-square-foot Leslie Shao-ming Sun Field Station, which opened last year, is constructed largely from recycled materials and designed to minimize its impact on the environment. The lead gift for the $3.3 million building was made by Anthony Sun in memory of his wife, Leslie, ’74, a former docent at the preserve. In early February, the station received the first annual San Mateo County Green Building Award.

When Cohen shows visitors around the station, he sounds like a kid showing off a new toy. “It’s really cool,” he says. The exterior is redwood siding recovered from demolished buildings in Escondido Village and Woodside. The insulation is recycled newspaper, millions of torn bits pumped into the walls. The bricks on the ground outside came from the basement of Leland and Jane Stanford’s campus home. And, since a significant percentage of carbon emissions worldwide comes from the manufacturing of cement, the concrete used for the floor of the building is made partly from fly ash, a waste product of power plants.

One of the first things noticeable about the field station is its massive windows. The double-paned, insulated glass keeps out heat but lets in daylight; no artificial light is needed until sundown. And several high-tech building features suggest Inspector Gadget has gone environmental. Solar collectors above the windows are tilted to maximize intake of sunlight, which is used to heat water in a tank inside the building, which is then pumped into wall radiators when the building needs heat. Photovoltaic panels on the roof, dark so as to blend into the hills, collect sunlight and convert it to electricity. “Our electrical bill is essentially zero,” Cohen says.

Cohen and the Rob Wellington Quigley architectural firm took care to select a site and position the building so that it would fade into the preserve surroundings. They were concerned that a standard pitched roof would make the building look big, Cohen says. So the designers inverted the roof into a V-shape. Since it formed a gutter, Cohen figured the field station should collect rainwater for study and use. A 25,000-gallon holding tank is being installed outside, and ultimately water will flow from the roof to pipes leading into the tank.

Inside the building, steel cables and trusses run between large steel columns at the ends of the building, keeping structural support along the periphery of the interior while using a minimum of material. The preserve’s research center finally has a home, in the center of the building, where lab benches stretch through a large open space. Two classrooms accommodate the more than 2,000 undergraduates who study at the preserve annually. In the rest rooms, there are, “of course, low-flush toilets,” Cohen says. “What would you expect?

“We did [all] this and it didn’t cost more” than using conventional building materials, he says. “It just means thinking through more and doing a lot of planning.”

“I think they did very well,” says John Hermannson, author of Green Building Resource Guide (Taunton Press, 1997) and a member of the San Mateo County award committee. “They thought about all the little details.”

That’s true right down to Cohen’s office, where his PowerMac G4 hums along on the electricity from the photovoltaic panels. Sure beats that Dodge pickup.

—BRIAN EULE, ’01

Inquiring Minds

GIVE FISH A CHANCE: In a January report for the Pew Oceans Commission, biological sciences professor Stephen Palumbi calls for immediate creation of marine reserves throughout the coastal United States. Palumbi cites a number of threats to healthy ocean ecosystems, including pollution, overfishing and runoff from land, and says there’s good evidence that small but fully protected reserves can play a key role in restoration. “When you have a reserve, fish inside get bigger, become more numerous and leak out the edges,” he writes.

HOT TOPIC: Every schoolkid knows that carbon dioxide is good for plants. But there’s such a thing as too much CO2, conclude researchers at Stanford and at the Nature Conservancy in the December 6 issue of Science. They simulated changes expected in the next 100 years due to global warming—increases of 2 degrees Fahrenheit and 50 percent precipitation, additional nitrogen deposits in soil and a doubling of atmospheric CO2—and observed that under those conditions, the additional CO2 actually retarded plant growth. They weren’t the only ones sounding the alarm. In the January 2 issue of Nature, Terry Root, a senior fellow at the Institute for International Studies, and her colleagues present a statistical analysis of 143 separate studies on global warming and biological change. “Birds are laying eggs earlier than usual, plants are flowering earlier, and mammals are breaking hibernation sooner,” Root says. Combined with loss of habitat, she adds, rapid temperature increase could wipe out numerous species.

HIGHER LEARNING? Although more people in the United States have access to higher education than ever before, policy makers need to examine the quality of the education they receive, says a new report by the National Center for Postsecondary Improvement on campus. “We are trying to create a sense of urgency in how well colleges and universities are meeting diverse needs and changing expectations,” says associate professor of education Patricia Gumport.

ECOLOGY

Finding Incentives to Conserve

STRIP MALLS aren’t the only unfortunate characteristic of suburban sprawl. Research associate professor of biological sciences Gretchen Daily, ’86, MS ’87, PhD ’92, and her colleagues recently reported in Nature that household size is shrinking worldwide, resulting in more housing construction per capita—and a concomitant increase in the use of land and materials, as well as consumption of water, fuel and other resources. All of which, the researchers conclude, threatens life-supporting biodiversity and habitat.

Daily’s broader passions are investigating the nitty-gritty science of ecosystems and winning advocates across disciplines for conservation. For 10 years, one of Discover magazine’s “50 most important women in science” has been tromping across the Central American countryside, trying to figure out what its flora and fauna tell us about the future of life on the planet.

STANFORD: What have you learned in Costa Rica?

There is a tremendous opportunity to harmonize our primary activity—growing food and timber—with conservation. What we are finding in Costa Rica is that many interesting birds, beetles, bugs, bees and amphibians can be sustained in human-dominated countryside. A lot lives there that people thought would be restricted to forest. We are finding that maybe 50 percent of tropical biodiversity seems able to persist in open countryside. One note of caution, though: that means at least 50 percent of animals and plants there can’t make it in the open countryside. That loss might be catastrophic.

You have brought people together across many disciplines to work on conservation issues. Why?

Everyone realizes we need the scientists there. We also need the economists to help you weigh choices, the lawyers to help design legal frameworks for making these decisions, and people in the business and policy communities to show how we might put theory into practice.

What has grown out of those efforts?

One new area is conservation finance. This has been something I’ve been getting into a lot. I wrote a recent book on it [The New Economy of Nature: The Quest to Make Conservation Profitable, with Katherine Ellison, Island Press/Shearwater Books, 2002]. Historically, we have seen conservation broadly defined as something we should take on as a charitable project or that there should be laws about. And overall, most things are headed in the wrong direction at an accelerating rate. The way some of us are trying to reframe this is to align with economic conservation. We are focusing on incentive-based strategies.

Is that sort of thing going to be effective everywhere?

I run a group at Stanford called the “Chocolate Group,” which includes people in all sorts of disciplines. The historical perspective is key, as is the perspective of diverse cultures. There isn’t going to be one blanket answer for the world.

IN PRINT

All in the Family

HE CALLS IT his accidental book. James Lock, associate professor of psychiatry and behavioral sciences and co-director of the eating disorders clinic at Lucile Salter Packard Children’s Hospital, was frustrated by the number of adolescent patients who relapse after hospitalization for the eating disorder anorexia nervosa. Then he heard about a unique therapy, developed in the mid-1980s at the Maudsley Hospital in London, that requires substantial involvement from patients’ families.

“When I read about it, I was a bit incredulous,” says Lock. Traditional anorexia treatments, he explains, often have a “bias against families,” regarding them as part of the problem. The Maudsley group, however, had successfully pioneered a “family therapy” in which parents worked as a team with health professionals to treat their child.

Lock and his colleagues received a grant from the National Institutes of Health to compare the effectiveness of the family therapy at durations of six and 12 months. With 86 subjects, it is one of the largest anorexia nervosa treatment studies ever, he says. As part of the project, the researchers created a manual for therapists to implement the treatment. “I wanted to write a manual that therapists could understand and do,” Lock says.

He spent so much time structuring the manual—setting forth what happens at each therapy session, then illustrating each step with examples—that at one point, he thought, “Maybe it’s a book.” And indeed it became one. Written by Lock, Daniel le Grange, Stanford psychiatry professor W. Stewart Agras and Christopher Dare, Treatment Manual for Anorexia Nervosa: A Family-Based Approach (Guilford Press, 2001) makes the Maudsley approach accessible to therapists worldwide.

The treatment requires parents to take control of food and weight out of the hands of their adolescent and expects them to determine the best way to feed their child. Siblings, too, are encouraged to find ways to support the patient. The ultimate goal is for patients to learn to manage their own eating.

The study’s results, which Lock characterizes as “robust,” will be available in April. Some anecdotal evidence of the treatment’s efficacy is already in. “What has so firmly convinced me is the fact that so many of [the patients] thank us when they recover and tell us that they couldn’t have done it any other way,” says Wendy Spettigue, psychiatric director of the eating disorders program at the Children’s Hospital of Eastern Ontario.

Lock is now working on a book for parents, due out in a year. This one, it seems, won’t be accidental.

Campus Notebook

Star Astrophysicists to Head New Institute

Stanford Linear Accelerator Center director Jonathan Dorfan calls them the “dream team.” This fall, Caltech astrophysicist Roger Blandford and Columbia physics department chair Steven Kahn will come to the Farm to serve as director and deputy director, respectively, of the new Kavli Institute for Particle Astrophysics and Cosmology. The institute is expected to bring together scientists from SLAC and the main campus to answer fundamental questions of physics. Says physics department chair Doug Osheroff: “This is the most exciting thing that has happened to physics at Stanford in the past 15 years, and that includes four Nobel Prizes in a row.”

Hennessy Reaffirms Affirmative Action

In a statement before the Faculty Senate on January 23, University President John Hennessy reaffirmed Stanford’s commitment to affirmative action in achieving a diverse student body. The Senate spontaneously and unanimously passed a motion of support for the statement, and applauded Hennessy’s intention to work with peer institutions on an amicus brief in the Supreme Court case about the University of Michigan’s affirmative action policies. “The consideration of race and ethnicity as one factor among many in [the] admission process is consistent with our history as an institution and our belief that the next generation of leaders must reflect the strengths and talents of all our nation’s citizens,” Hennessy’s statement read in part.

For the Eastern Trail, a Step Toward Resolution

In December, the Santa Clara County Board of Supervisors voted to proceed with environmental review of three possible eastern trail routes on Stanford land, dropping consideration of a fourth route that University administrators had called too intrusive, and allowing consideration of a fifth route only if the first three prove infeasible. Under the terms of its 10-year General Use Permit, Stanford is required to dedicate two trails for public use: an eastern one near Page Mill Road and a western one near Alpine Road.

Trying to Keep Tuition Increases in Check

It’s a dilemma: how much to raise fees when both the University and students’ families are hit by the slumping economy? The Board of Trustees settled on a 4.8 percent increase in undergraduate tuition, room and board, which will total $37,613 in the 2003-04 school year. “It’s slightly less than [last year’s 4.9 percent increase], which I think is good under the circumstances,” says board chair Isaac Stein, JD/MBA ’72. He also points out that “in an economy like this, you give back much of your nominal tuition increase in the form of higher financial aid.” Most graduate students will see a 5 percent tuition increase; tuition at the Graduate School of Business will go up 8.9 percent.

SEMINAR ROOM

In Judaism, 'What Is Legitimate Violence?'

“HIS HEART ROSE TO CRAZINESS,” one student began, tracing the Hebrew words with his finger as he read aloud.

“Yesssss,” the professor said, slowly. “Or we could say, ‘He became obsessed with her.’ ”

The seven undergraduate and graduate students enrolled in the seminar Judaism and Violence hunkered over photocopies of the Babylonian Talmud as they took turns parsing the rabbinic commentaries in Hebrew and Aramaic. Most of them had taken courses with Charlotte Fonrobert before, but this was their first encounter with a primary text of such magnitude.

Fonrobert, a native of Germany and a specialist in the field of academic Talmud study, came to Stanford as an assistant professor in 2000 after teaching at the University of Judaism in Los Angeles. Her new course could have been a dry exercise in legal semantics, and her requirements—that students prepare translations of 2nd-century texts and be ready to discuss them in the context of current scholarly literature —could have assumed the weight of centuries of rabbinic discourse. But Fonrobert’s casual asides (“Never mind that Esther saved the Jewish people!”) set a lively tone and encourage sharp analysis. “What’s the logic here?” she will ask. “You’ve got it right, but it doesn’t quite make sense, does it?”

John Mandsager, who is completing a master’s in religious studies, is part of a weekly study group that struggles through the assigned texts, word by word, with dictionaries in hand. “Professor Fonrobert is down the hall to answer any pressing questions about Aramaic prepositions, and to laugh at our extended conversations about what the rabbis were saying about the biblical character Esther,” he says.

Fonrobert cites two acts of violence committed in the name of Judaism but prompting outrage in Israel—the 1994 machine-gun killing of 29 Muslim worshippers in Hebron by a member of a fringe settler movement, and the 1995 assassination of Israeli Prime Minister Yitzhak Rabin by a student affiliated with right-wing extremist groups—that got her thinking about someday teaching a course on Judaism and violence. “When violence was dealt with in Jewish studies, I think it was mostly in terms of violence against Jews, which has an historical basis from the Crusades to the Holocaust,” Fonrobert says. “But there is now a debate about religion as a source of violence, and we’re asking, ‘How does Judaism fit into that? Is the only story that Jews throughout most of their history were victimized?’ ”

In their deliberations about sentencing Rabin’s killer, Israeli trial judges cited rabbinic law in the Mishnah, a 3rd-century text that forms the basis for all subsequent developments in Jewish law. Fonrobert was familiar with the ambiguities of texts from that era and thought they could serve as a basis for intriguing conversations about the ethical consequences of one’s religious beliefs. “The debate is similar to the response to September 11: what is true Judaism or Islam?” she says. In her course, students use both the Talmud and current scholarly monographs to explore such issues as martyrdom, war, and what Fonrobert calls “verbal” violence and “gender-bound” violence. “There is a long discussion in the Talmud about for what should we be willing to die,” she says. “Are you allowed to kill yourself? What is legitimate violence?” The final exam: a one-hour conversation with the professor.

Brian Decker, a junior majoring in religious studies, didn’t know the Hebrew alphabet when he signed up for the course, and he says he doesn’t consider himself deeply religious. “Questions of God and the universe, good and evil, have always been secondary in my mind to the study of how people have interpreted those issues, how cultures have answered those questions.”

Which is precisely the focus of Fonrobert’s course. “I think in general one can say that rabbinic Judaism values survival at all costs, and there cannot be such a thing as celebration of death,” she says. “I also belong to the school of thought that says we can really only talk about Judaism as we know it with the inception of rabbinic Judaism in the 2nd century. Can we do that in 10 weeks? That’s where the experiment lies.”

What You Don't Know About Teaching Assistants

FOURTH-YEAR GRADUATE STUDENT Julie Heiser has served as head teaching assistant for Psychology 1, and has TA’d cognitive psych and developmental psych. It’s not the worst job she’s ever had. Or the best.

The TA job description is long. Without a TA to corral the handouts, slides and audiovisual equipment needed for a large lecture class, says Heiser, “the course is going to bomb.” She’s even had to run upstairs and tell a professor that he’s running late. “A course is a production, and it’s also a venue for the professor to show off his talents and stuff. But along with that come enormous amounts of things to do.”

TAs take the heat. Have you heard the one about the professor whose overhead-projector pen ran out of ink? “He said, ‘Do any of my TAs have an overhead pen?’ ” Heiser says. “And they were like, ‘Why would we carry overhead pens?’ And he was like, ‘Shows you how prepared my TAs are.’ ”

TAs dream about their job. And not necessarily in a good way. “When [students] write essay exams, they write the same things over and over again,” Heiser says. “Like, first this person blah blah, then this person blah blah, therefore blah blah blah. I wake up in the middle of the night reciting these things over and over in my head, and it drives me nuts.”

Complaints? Special needs? See your TA. If a student has a problem, the TA is often the first stop. “And a lot of us come from public schools where, hell, no, if you don’t show up to the exam, you get a zero—there’s no exception.” But on the Farm, says Heiser, “we have to make every exception because Stanford spoils its undergraduates.” Oh, and it’s the TAs who fax exams to student-athletes on the road and make sure they return them in time. “It’s not that big of a deal—we’re just kind of waiting around for an hour—but I also can’t imagine it happening anywhere else.”

TA complaints? The usual. Fraternity pledges running naked through a lecture hall or vomiting in the front row.

There’s a certain amount of learning on the job. The Center for Teaching and Learning presents a one-day seminar for new TAs, but otherwise there’s little training. “You’ve been in so many classes that you’re kind of familiar with the role of the TA,” Heiser says. “But still, it’s hard to all of a sudden be in that role. You’re kind of thrown into it.”

TAs need fashion consultants. Undergraduates tell Heiser they can spot a TA across the Quad. “They tell me we walk with our heads down, and we look frumpy and unhealthy,” she says. “I think their perceptions are accurate in some ways—we’re definitely frumpy.”

TAs want to help, but . . . “Students expect to get good grades without working hard—and the grades are already inflated,” Heiser says. Those aiming for law school, she adds, tend to freak out if they get a B. “It’s like the end of the world. You want to help them, but you can’t. They deserved that B.”

Psych TAs don’t diagnose their students. Do they? “Do we diagnose students? No, no,” says Heiser. “Well, I mean, yeah, we do. We know a lot about what people go through as undergraduates, and I think we have an added intuition about what’s really going on and what their motivations and social pressures may be.”

The job has rewards. Sometimes. “What’s so wonderful for the TAs is when you kind of nurture a student into becoming interested in your field,” Heiser says. “I’ve had a couple of students in my sections who have gone on to do research in the department, and that’s rewarding.” She pauses. “But mostly it’s about grades or athletics.”