Persuasion Power

® Rory Daniel

As a teenager living in San Francisco, Edison Liu taught himself how to hypnotize people. "I pulled some books out of the public library, read up on it, and tried it on my friends"ﾠ-ﾠincluding the kids at the summer music camp he attended. "The peak of susceptibility is during early adolescence," says Liu. "So I could get these guys to actually hallucinate. They loved it."

Their parents, however, did not. Liu got called out during the end-of-summer concert after directing the chorus members to collapse on the stage, one after another. "In my delusion, I thought that maybe I had gotten an award and they needed to inform me," says Liu. "Instead they put me in a car with one of the parents who was a clinical psychologist who interrogated me about my experiences with their children. From that day on, I never hypnotized anybody."

Maybe not directly. But as the founder and executive director of the Genome Institute of Singapore, Liu continues to have a powerful influence on his peers. "Ed's a very smart guy, and he's especially smart interpersonally. I think these days it's called a high emotional IQ," says Ray White of the University of San Francisco's Gallo Center. "He's able to connect with people, understand what they're thinking, and get them to work together to meet the needs of the institution." In Singapore, says White, Liu has brought together "people who are brilliant DNA mechanics at the bench with people who have a biological problem to solve, along with the computational guys who then make sure you're not speculating your way out to the moon. To do that requires a lot of insight and an ability to communicate effectively with people."

"He's also an incredibly charming guy," adds Morris Birnbaum of the University of Pennsylvania. "You can't underestimate how much that helps when you're trying to ingratiate yourself with folks and get them to work with you."

Working with colleagues, mentors, and trainees, Liu has identified a novel class of receptor tyrosine kinase involved in human leukemia, sequenced the SARS virus, and exploredﾠ-ﾠeven exploitedﾠ-ﾠthe constellation of changes that define breast cancer. He now shares that expertise with some 300 students and young investigators at the institute he helped establish less than 10 years ago.

Liu has a longstanding interest in all things psychological. He graduated from Stanford University in 1973 with a dual degree in chemistry and psychology. "It was an indication of a psychiatric condition I call dilitantism," says Liu. "I loved learning about different things and never kind of figured out that I needed to be deeply involved in anything." As a medical student at Stanford, Liu continued to dabble, spending a summer in China on a Ford Fellowship doing an intensive study of Mandarin Chinese, teaching a course on the sociology of overseas China, and taking a year off to do research on the pharmacology of general anesthetics.

He enjoyed the research, but studying problems with such direct relevance to human health and sicknessﾠ-ﾠsuch as the metabolism of anesthesia or chemotherapeutic drugsﾠ-ﾠwas not Liu's cup of tea. So after completing his medical trainingﾠ-ﾠincluding an internship and residency at Washington University in St. Louis, followed by a fellowship in oncology at Stanfordﾠ-ﾠLiu tried his hand at basic research in the laboratory of J. Michael Bishop at UCSF. "It was a whole new world," he says. "Rather than thinking of disease as an endpoint, disease was now simply a system you worked on to understand the fundamental rules of biology. If you got something practical out of it, great. But that wasn't why you were asking the question. That was a profound experience for me."

In the Bishop lab, Liu focused on leukemias and published a few papers fingering ras genes as being key players in those cancersﾠ-ﾠ"not very interesting by then" because the connection between ras and cancer had already been established. In those same assays, though, he also turned up one gene that wasn't part of the ras family. Once he'd established his own lab at the University of North Carolina in 1987, he cloned that gene and discovered it encodes a novel type of receptor tyrosine kinase.

Although he and his lab continued to characterize that protein, called Axl, Liu broadened his focus to look at other tyrosine kinases involved in breast cancer. "When Ed fishes out a protein, he doesn't want to spend 20 years working only on that protein. He wants to understand what's wrong with a breast cancer cell," says fomer postdoc Andreas Neubauer, now at the University of Marburg, Germany. That desire made him a rare hybrid between a molecular biologist and a clinical scientist.

"In those days it was much more unusual for a medical oncologist to have real basic science training," adds UNC's Shelley Earp. "But learning molecular genetics from the ground up has served Ed well. He's been able to put together that fundamental training with his dedication to oncology to become one of the leading people in cancer genetics."

At UNC, Liu essentially ushered in the era of molecular epidemiology, promoting the use of new technologiesﾠ-ﾠsuch as quantitative PCRﾠ-ﾠto do tumor profiling. "Ed really led the way to using science to better identify which patients will respond to treatment," says UNC colleague Lynn Dressler. For example, in the early 1990s Liu and others began screening breast tumors for the presence of Her2, a protein that was shown to predict a patient's response to specific forms of chemotherapy. "We now call it pharmacogenetics with somatic tissue. But Ed had the foresight to know that it was possible to do it then."

"One of his great strengths was to recognize early on that the way we'll make progress in treating cancer is to understand its fundamental biologyﾠ-ﾠto take what we learn in the laboratory and use that to develop better treatments for patients," says Richard Schilsky of the University of Chicago. "It seems sort of obvious now. But it took a long time before we learned enough about the basic biology of cancer to even conceive of how we'd use that information. But Ed was always particularly good at making those kinds of conceptual leaps."

He was also good at attracting funding. In addition to helping UNC land a coveted SPORE grant for interdisciplinary, translational research, by 1996 Liu was sitting on $2.5 million in funds. That's when he got the call from Rick Klausner, inviting him to become the National Cancer Institute's new director of clinical sciences. "What attracted me was scale," says Liu. "By then I was starting to develop a philosophy of where the field should be going and I was seeking an instrument to be able to execute some of those philosophies. And NCI was the largest instrument around I could see."

There he set his sights on functional genomics, sending his graduate student Lance Miller to Pat Brown's Stanford lab to learn about building microarrays. When Miller returned, Liu made him director of the NCI's new array facility. "We started off small," recalls Miller. "Our first facility was literally in a big closet in building 10." But over time, Liu built an advanced technology center that provided investigators sequencing and proteomic technologies, as well as what Miller calls "an A to Z solution for microarrays."

"It was a big deal to have access to arrays," says Amgen's Lanny Kirsch, who worked at NCI at the time. "You couldn't just call up and have them sent to you like you can today. Ed brought a genomics perspective to NCI's intramural program."

In 1999, he also helped broker an agreement that brought together parties from Ireland and Northern Ireland to restructure their cancer training and clinical trial programs. "The All Ireland Cancer Consortium has transformed the whole landscape of cancer care on the island of Ireland," says Patrick Johnston of the Queen's University of Belfast, a former NCI investigator who approached Liu for help fleshing out a workable program. "Ed was really instrumental in bringing the whole thing to fruition."

Part of what he learned from working with the Irish, Liu says, "is just how powerful symbols coming out of a small nation could be for the world. And I realized that you can do great things in a small country that would have an impact far beyond your weight." So when Philip Yeo, then head of Singapore's Agency for Science, Technology and Research, invited Liu to join the team, he couldn't say no.

The move was good for Liu and good for Singapore. "What he's done in the past six or seven years to build a really world-class genome research institute is just astonishing. I continue to be blown away by the accomplishment," says White, who's on the Genome Institute's scientific advisory board. Birnbaum agrees. "He started with nothing. There are a lot of people who go to institutes and become director and make it better than before. But it's very rare for a person to go to a place where there's literally nothing and build it from scratch."

Since its inception, Liu has taken the Genome Institute of Singapore from a three-person operation into a booming hub of genomic research that boasts about 300 members and more than 350 publications, many in top journals. "This is a group that didn't even exist before 2001. Now they're publishing in Cell and Nature and Science. It's really very, very impressive," says Birnbaum. "They're smart, creative, and doing stuff that really matters."

On the whole, the institute nucleates around transcriptional regulation and transcriptome profiling, particularly relating to stem cell biology or cancer. In one study, for example, investigators mapped the p53 binding sites in the human genome, work published in 2006 in Cell.

And Liu still manages his own lab, focused on studying estrogen-receptor signaling in breast cancer cells. He's also working on technologies that will allow him to identify fusion genes that might be responsible for solid tumors. When he's not doing all thatﾠ-ﾠor performing his duties as head of the Human Genome Organization and half a dozen other Singapore-based agenciesﾠ-ﾠLiu is trying to figure out how to get the Genome Institute to function like an orchestra, so that the big-picture biologists and the informatics whiz-kids and all the brilliant hands at the bench can work together "to make beautiful music," as he puts it.

If anyone can make that happen, it's Liu. "At some point during my wedding reception, I look over and there's Ed, jammin' on the piano with my stepson and a couple of his friends," says UNC's Dressler. "He's smiling and having a grand old time."

Says Liu, "It's not so bad to be a dilettante."