Scientist Seeks the Cause of Diseases

Dr. Ian Lipkin pulls out a printout from an Internet listserv where doctors around the world report on infections that have them mystified.

“These things come out all day long,” said Lipkin, head of UC Irvine’s Emerging Diseases Laboratory. “No one has any idea how to deal with [them].”

Lipkin, who founded the lab at UCI in 1990, is an explorer who, along with other researchers, hunts for unidentified microbes, trying to figure out which illnesses are caused by which viruses.

It was Lipkin who, in 1999, identified West Nile virus, previously unknown in the United States, as the cause of the encephalitis outbreak that killed seven people in the New York City area. The discovery catapulted the UCI physician and professor of neurobiology into the scientific spotlight and sent him to Japan, Germany, France, Italy and across the United States, attending conferences and collaborating with other researchers.

The West Nile discovery was the kind of research Lipkin thrives on, delving into the mysterious world of disease and turning up a cause. Working at the frontier of molecular biology, he seeks microbes he believes are responsible for a number of chronic diseases, including multiple sclerosis, autism, Alzheimer’s and depression.

But in his UCI office, a weathered leather doctor’s bag sits on a bookshelf and cardboard boxes are stacked in the corner, boxes he is packing to move to Columbia University. There, he will join the faculty of the Mailman School of Public Health, drawn by the more extensive facilities the Ivy League school can offer and the closeness of premier researchers in New York.

“He’s a star,” said Allan Rosenfield, dean of the Mailman School. “His work on West Nile is just one indication of the high caliber of work he’s engaged in.”

Already Lipkin is commuting between the coasts, spending most weekends in the Upper West Side brownstone where his girlfriend and their two children have moved from their home in Laguna Beach.

He talks excitedly about going to Lincoln Center for the Mostly Mozart Festival and the greater scientific collaborations available in New York.

“He loves to travel,” said David Relman, a friend and professor of infectious diseases and microbiology at Stanford University. “He likes the thrill of seeing or doing something for the first time. [He’s] a true kind of experimentalist in terms of life experiences.”

Research Facilities Tempt Star Academics

Top academics often are tempted by offers of more money and better research facilities. Brian Mahy, another friend and a senior scientist at the National Center for Infectious Disease, said the professor felt he wasn’t receiving the kind of institutional support he needed at UCI, including a secretary.

“He had expressed to me two or three years ago he was feeling itchy and looking at a few other possibilities,” Mahy said.

For Lipkin’s use, Columbia is converting two floors of a 1926 building on its Health Sciences campus, a total of 6,300 square feet. From his 19th-floor window, Lipkin will look out on the Hudson River and the George Washington Bridge.

“It’s a major statement of Columbia’s support for his work and research,” said Catherine Murray, the Mailman school’s associate dean for external affairs.

Thomas Cesario, dean of the UCI College of Medicine, said the university tried hard to keep Lipkin. “I think it’s a sign of our growth that people like Ian get offers,” he said.

Cesario said medical schools are being squeezed financially. “I don’t know what was offered in New York, but these are not easy times in academic medicine,” he said.

A Reputation for Cutting-Edge Work

Lipkin is an attractive recruit for any university. At 48, he’s relatively young, with a reputation for cutting-edge research. He’s a compulsive worker, who often works through the weekends.

“He calls me up at all hours of the day and night, and is extremely dedicated to his subject,” Relman said.

Lipkin grew up in Chicago, the son of a psychiatrist. He received his bachelor’s degree from Sarah Lawrence College in New York, becoming one of the first men to spend four years at what had been a women’s school.

When Lipkin entered Sarah Lawrence, he was interested in mythology, philosophy and cultural anthropology and curious about other parts of the world. But his organic chemistry professor made the subject come so alive that Lipkin turned to science. Still, at that time, Sarah Lawrence’s only degree was a bachelor’s in liberal arts.

When the 1974 graduate delivered the commencement speech to Sarah Lawrence’s class of 2000, he told them, “Many of the concepts I now use daily in molecular biology and neuroscience are rooted in lessons learned” from his liberal arts studies.

“Perhaps the most important of these is that models are constructs that must be adapted with accumulation of new data,” he said. “Having a historical perspective on how paradigms emerge has encouraged me to take on projects others thought undoable and to recognize that research is most exciting when the facts don’t quite fit.”

He received his medical degree from Rush Medical College in Chicago.

While he was a neurology resident at UC San Francisco in the early 1980s, two things set the stage for his career in what he calls “pathogen discovery.” The first was the emergence of patients diagnosed with the then-mysterious disease AIDS.

The second, he told the Sarah Lawrence students, was the discovery of prions, an infectious molecule in the membranes of cells that is neither a bacterium nor a virus. Prions are thought to spread mad cow disease.

Lipkin said he was inspired by the discoverer of prions, Dr. Stanley Prusiner, a professor at UC San Francisco, who “pursued an iconoclastic hypothesis in the face of public ridicule.”

Prusiner received the Nobel Prize for medicine in 1997.

Lipkin got involved in the search for a disease that was killing people in New York when state officials sent him brain samples of four who had died. West Nile had caused encephalitis in Europe, Africa and the Middle East, but until 1999, had not been identified in the United States. Most people infected with the virus suffer flu-like symptoms and recover. But the very young, the elderly and those with damaged immune systems may be threatened.

By studying the genetic sequencing of the virus, Lipkin identified West Nile as the cause of the encephalitis outbreak. He and his team then developed a simple test to detect West Nile in a small sample of spinal fluid in just five hours. Results from a previous test took three to four days.

Lipkin and his team won national attention, and their main work was showcased: taking tissue and using techniques of molecular biology to search for unknown viruses and bacteria, and determining which diseases are caused by known microbes.

“When people can’t figure out what’s going on, they get in touch with us,” Lipkin said.

He calls it the Pandora’s Box Program.

“Our hypothesis is we will discover new agents by this approach,” Lipkin said. “Until you know something exists, how can you implicate it in a disease?”

For example, the causes of about 70% of encephalitis cases, an infection of the brain, are unknown, “probably because it’s being caused by viruses we don’t know about,” Lipkin said.

He also theorizes that many diseases result when a pregnant woman is infected with a microbe while the fetus is in a particularly vulnerable stage. That may be enough to cause the disease later in life or to affect the fetus if something in the environment triggers the microbe.

“We know tobacco and alcohol can damage a baby,” he said. “Why not infectious agents?”

The theory is becoming increasingly popular, especially since it was discovered that a bacterium causes peptic ulcers. “We’re beginning to understand how things interrelate,” Relman said. “You can’t cure something until you find out what’s at the bottom.”

Lipkin Looking at Mental Illnesses

Lipkin has stepped into an ongoing controversy over the causes of mental illnesses. Some researchers think schizophrenia, depression and bipolar disorder are caused by the Borna virus, which causes encephalitis in horses and behavioral problems in other animals.

Lipkin and his team were the first to isolate the virus in human brain tissue. But just because the virus causes disease in animals doesn’t mean it reacts the same way in humans.

Studies on the relationship between Borna and mental illness have come to varying conclusions, with some researchers finding a connection and others finding none.

Now Lipkin and his researchers are involved in a $3-million study to determine the relationship between the virus and mental illness.

C.J. Peters, a professor in the department of microbiology, immunology and pathology at the University of Texas Medical Branch in Galveston, doubts that Borna causes mental illness. Peters is an expert in another branch of emerging diseases, the deadly Ebola virus.

Still, he supports Lipkin’s work.

“I think it’s where we ought to be,” Peters said. “The thing about Ian is, he’s a very smart guy, and he puts things together. He decides what needs to be done and he goes after it. He’s gone out to find out what’s going on [at] the edge of the frontier.”