Caltech News, Vol. 33, No. 1, 1999

Alice Huang: Keeping Science and Life in Focus

By Hillary Bhaskaran

Alice Huang in the lab in the early 1970s and joined by her husband, David, and their daughter, Lauren "The Kid" Baltimore, in 1975.

 

Not all experiments end up the way you plan. Alice Huang, a scientist, wife, mother, educator, dean, and now Caltech's first lady and councilor for external relations, first set out to be a doctor.

Even before she moved from Kiangsi, China, to the United States at the age of nine, she had set her sights on the medical profession. "And my father didn't say I couldn't do it," Huang recalls. In fact, her father had unwittingly inspired her career interest.

Having been orphaned in Anhui, China, at the age of 12, Huang's father, Quentin K. Y. Huang, had been taken in by missionary John Shryock and educated at the University of Pennsylvania and Philadelphia Divinity School. He became a minister and later an Anglican bishop in China, where he married Huang's mother, Grace Betty Soong, the child of a large landholding family from Kiangsi Province.

Grace's life had also been influenced by missionaries. Her father felt that conversion was a small favor to grant the missionaries who had come so far to build schools and hospitals. So he allowed every other one of his children, including Grace, to be christened in the church rather than remain Buddhist.

"Don't work with Jonas Salk," said the hotshot virologist. "Work with me, and bring your own money."

Raised in this Christian family, Huang remembers that her father "would ruefully say, 'It seems if I had the chance to redo my life, I would save bodies and not souls.'

"That stuck," she says. After two years at Wellesley College, Huang enrolled in 1959 in a 2/5 program that brought her to the medical school at Johns Hopkins University. "College was expensive, and I was eager to get on with my life," she says. But along the way she got more interested in the research aspect of medicine and less interested in aspects requiring endless routine and strong stomachs. "I never minded blood," she says, but on the day someone was needed to deal with a drunk on the street who was in danger of gagging on his tongue, Huang found that "I didn't want to go touch him. I realized that's not a good thing for a physician to think."

Huang received a BA in human biology from Johns Hopkins in 1961 and went on to earn an MA and PhD in 1963 and 1966, both in microbiology. As a graduate student, she became an expert virology researcher, purifying and analyzing the components of the vesicular stomatitis virus (VSV), a disease that spreads quickly among cows and horses and causes severe blistering. Her original goal had been to use VSV to produce interferon, an antiviral protein, to better understand how cells fight viruses. But along the way, Huang discovered something more interesting.

While purifying the virus for her studies, she says, "I found two beautiful bands"—one containing long, bullet-shaped particles consisting of the fully infectious virus, and the other containing short bullets, consisting of something that looked like the virus but hadn't been identified. Huang set out to characterize these defective interfering (DI) viral particles and was the first to determine that they inhibit the growth and replication of standard VSV in a cell. This phenomenon has since been identified in almost all other viruses and is being explored for its potential to control viral development, especially in plants.

ENTER THE "HOTSHOT VIROLOGIST"

When Huang went to present her first paper at a conference in 1965, she happened to meet David Baltimore through a mutual friend. Then a postdoc at Albert Einstein College of Medicine, Baltimore "was already a well-known hotshot virologist at the time," says Huang. That was that, until Huang started looking for a postdoc position and was considering approaching Jonas Salk, the discoverer of the polio vaccine who had founded the Salk Institute for Biological Studies in San Diego, California. "I realized that David was in Renato Dulbecco's lab there, so I wrote to ask him what the situation was like in Salk's lab." After gathering a reference on Huang, Baltimore gave the aspiring postdoc this advice: "Don't work with Jonas Salk. Work with me, and bring your own money." This was not the start of their romance, but Huang did decide to join Baltimore's lab in 1967. Drawing on her VSV expertise, Huang and Baltimore were on the brink of understanding more intriguing processes at work in viral replication. But then "David was off to MIT" within a year of Huang's arrival at the Salk Institute. "I didn't want to go east again," says Huang, but colleagues advised her not to let a good project go. After relocating with Baltimore, she adds, "we got to know each other a lot better." They were married after nine months at MIT, in 1968.

Getting back to viral replication, Huang, Baltimore, and graduate student Martha Stampfer found that VSV entered a host cell as a single negative strand of RNA. They knew that a smaller, complementary positive strand of RNA was capable of making an enzyme that facilitated the transcription and replication of more RNA. But the incoming negative strand of the virus was not capable of making this enzyme, known as RNA polymerase. This led the team to wonder how the VSV infection could get started since transcription was the very first step. They found that VSV brought its own RNA polymerase into the cell along with the negative RNA strand in order to start the process.

Huang sits with her mother in China in 1948 (top photo) and sails with her daughter in the late 70s (bottom left photo). In 1998, she meets freshmen at a reception in the garden of the president's house (righthand photo).
 

Baltimore would soon discover another distinct class of viruses that bring companion enzymes into a cell, much like VSV with its polymerase tagalong. But this newly discovered enzyme, later named reverse transcriptase, allowed the virus in question to turn viral RNA strands into viral DNA strands. The viruses that fall into this category, later dubbed retroviruses, include HIV, the virus responsible for AIDS.

Where was Huang when her husband, David Baltimore, was taking their early RNA research to a level that would soon win him a Nobel Prize? "I was job hunting," she says. "I called him after giving a seminar at Boston University, and he said, 'It's 50 counts over background," referring to the presence of the then-unnamed reverse transcriptase. "I think it's real.'"

"IT WAS TIME TO GET MY OWN JOB"

Huang learned more than science during her postdoc at MIT. "It was the late sixties, and we realized that women had opportunities. Staying in someone else's lab [could be problematic), especially if you had good ideas and wanted to work on your own." At least one highly respected MIT scientist who had remained in a subordinate research associate position discovered the drawbacks.

"Anna Marie Torriani-Gorini was internationally known. Students and postdocs vied to work with her," says Huang. Content to remain a research associate at MIT, she relied on her affiliation with a professor to support her research team. But when her professor left MIT, Torriani-Gorini was not only ineligible to host students and postdocs, but she also couldn't get grants in her own name. Huang supported her colleague's belated fight to be made a professor, a request later granted to the 55-year-old scientist.

Torriani-Gorini's experience "affected a whole generation of young women in the biological sciences," says Huang. "Women realized this was not the route to go, where you tied your future to someone else's star, perhaps moving your whole family around" to follow that person. Huang realized that "if something happened to David or if we were divorced," she could find herself in a similar situation to that of her colleague.

So she chose a different path, making a name for herself over the next two decades as she climbed the professorial ladder at Harvard Medical School. And she always kept another female mentor's advice in mind.

During her early days at Harvard, Huang visited Polly Bunting, a Johns Hopkins graduate who had become president of Radcliffe College. Bunting urged Huang to "really focus on your career and publish, get tenure and become a professor, and don't get sidetracked by all the committees they'll try to put you on because they want a woman. But once you become a professor, don't forget you're still a woman."

Indeed, says Huang, "I've seen people who have lost their femininity and feminine instincts." Bunting also suggested that Huang keep a shoe box of names of interesting women in science so that when people say "There's not anyone good I can hire,' you can throw it in their faces." Huang has kept track of people and says, "I've certainly referred a lot of women to jobs."

Once established as a professor of microbiology and molecular genetics, Huang says, "I thought I'd be at Harvard for the rest of my life." But by 1990 Baltimore was off to New York, where he'd been named president of Rockefeller University, and Huang was offered a position as dean for science at New York University. Not knowing whether she'd like full-time administration, she took the job on the condition that she could continue her research while at NYU. It was during this time that she often wondered how much one person could take on, and she learned how to delegate and let go of things (including the research dimension of her job by 1995).

In the world of administration, Huang had already served as a director of the Laboratories of Infectious Diseases at Children's Hospital in Boston. While there, she was the first to demonstrate that HIV, like other enveloped viruses, can alter the proteins of its surrounding membrane or envelope by incorporating those from another virus in order to fool host cells into thinking (chemically speaking) that it is not HIV.

As Huang settled down and set her priorities in New York, Baltimore found himself heading back to MIT after a tumultuous few years at Rockefeller. Embroiled in a scientific fraud case at the time, Baltimore defended a colleague's honesty at considerable expense to his own reputation. (The case has been covered in great depth, most recently in The Baltimore Case: A Trial of Politics, Science, and Character, by Caltech professor Dan Kevles.)

"It was a terrible period," says Huang, who nevertheless tries to keep it in perspective by considering the lessons learned and shared from a politicized struggle smacking of McCarthyism. Huang adds that, "as I told Dan, after escaping from the Japanese during World War II and piling our family's belongings into a steam-driven truck with five other families bound for Tibet, I think I've learned how to handle suffering."

With her husband back at MIT, Huang began commuting and telecommuting between Boston and New York City to continue her job at NYU. She scheduled meetings from breakfast through dinner during three-day stints in New York. Flying back to Boston in two hours' time, she took calls that were patched through by her secretary at NYU. "It was an extraordinarily efficient way to work," she says, "and David and I really appreciated getting together. I support that way of working and commuting for duo-career families. Of course we were spoiled, we had housekeepers at both ends." Throughout her career, Huang says she has kept "a focus on the things I enjoy doing," not feeling that she had to have a job. "I've been lucky."

"I CERTAINLY DIDN'T PLAN THIS"

Was the decision to pack up and move to California a difficult one? "Yes," she says. "I said I never wanted to live in L.A. It's such a desert." But the people on the presidential-search committee, especially Professor Kip Thorne, turned the tide. "They gradually introduced us to Pasadena," asking for no commitment, says Huang. "We didn't know much about Caltech; it was always that other school."

Now that it's their school, and as they settle into the president's house, Huang considers her newest milieu. "I'm in the throes of how best I can use my time. I'm hoping that as councilor—in the first part-time position I've had—I'll have a chance to explore. The board of trustees wanted very much for me to be close to Caltech in its relationship with sister institutions and with agencies in the federal government that fund science research. Those are broad mandates."

As councilor for external relations and a faculty associate in biology, Huang will lend her 20-plus years of experience in medical schools and research universities to Caltech's Biological Sciences Initiative. As she sums it up, "BSI means a lot of energies are going into making biology better than it ever has been, if that is possible, applying interdisciplinary approaches and methodologies toward a particular problem." Cooperation with medical institutions such as UCLA, USC, City of Hope, and Huntington Memorial Hospital will be key as Caltech develops an MD/PhD program-exposing Caltech students to medical applications in addition to exposing medical students to Caltech research—and as it capitalizes on opportunities for data sharing and research collaborations.

Huang sees herself as an "institutional capacity builder" who gets the right people together "around the right ideas at the right time." Collaborations and programmatic grants, for instance, are not dictated from the top down," she says. With "long-term capacity building, it may not seem obvious that relationships have been built, but when opportunities come up, you can be perfectly positioned to take advantage of them." Huang says she has the luxury to focus on the long term, since she doesn't have payroll and related administrative responsibilities.

In her "spare time," Huang is serving as a trustee for the Keck Graduate Institute of Applied Life Sciences, a new school that's part of the Claremont Colleges consortium. She was offered that position as soon as word got around that Baltimore was coming to Caltech. Huang has also been invited to join the Pacific Council on International Policy and the Blue Ribbon, which supports the Music Center's resident companies.

Elsewhere, she chairs the scientific board for the Institute of Molecular Cell Biology in Singapore, succeeding Sydney Brenner, who together with Huang and top Singaporean scientists established this modern research institution. She sits on several boards—Johns Hopkins University, the Keystone Center, the Foundation for Microbiology, the American Association for the Advancement of Science, and the Health Effects Institute—and is a member of the FDA advisory committee for vaccines.

Such a full life suits her and her husband, she says, and it fulfills their shared interest in "being around intelligent people. Basically our philosophy of life is very similar," she adds. "We believe in living life to the fullest, in constantly learning new things, and in using one's brain to benefit the world we live in."

Take them out of their day-to-day setting and Huang finds at least one notable difference between her and Baltimore. "When we go on vacation, I really like to veg, but he likes to tire himself out doing things. Our daughter says, 'Dad really vegges fast.' For instance, when we go to Montana for a long weekend, there is usually a lot of scientific talk with colleagues, [mixed with] a lot of fishing and good eating. In four to five nights we may stay in three to four different places." There's no sitting by the pool, she adds.

Their 24-year-old daughter, Lauren, whose nickname Teak comes from "TK" or "The Kid," has apparently adopted a similar lifestyle. "She seems awfully busy," says Huang. A graduate in psychology from Yale, Teak is starting a company in New York City to design and maintain Web pages, especially for TV series. She has already designed an award-winning Web site for the Generation-X show Party of Five.

Huang also has an interest in the entertainment field, both as an educational vehicle and as a way to show the human side of science—the natural, real-life stories." The main character of a would-be TV series was modeled after her. Called The Dean, this brainchild of Nobel Laureate in physics Leon Lederman was scripted by a group of scientists, including Huang. "We've wanted a science program in prime time, like NYPD Blue or ER, that isn't fantasy like The X-Files, that would have comedy, blood, gore, and sex, as well as science," she says. As with scientific research, the next stage of this project awaits funding.

And the sequel to Huang's real-life story? She's looking forward to learning from her experience here and hopes "to leave behind something that will be of value." Beyond that, "I'm always surprised that life holds so many twists and turns," she says. "I've never been good at predicting the future."