Twenty-five years before she helped solve a mystery behind one of the world's most common cancers, Michele Manos was a kid dripping diluted aspirin into a pet mouse whose neck bulged with an ugly tumor. She hoped to stop the pain.
When the mouse died, the 11-year-old from Flint, Mich., did the next logical thing. She performed an autopsy, slicing the tumor with a crude cutting tool from the family art supplies.
Studying the malignant mass, she wondered what caused it. Her mother's smoking? Fumes from paint cans kept near the mouse cage?
"I was back then trying to figure out what caused cancer," Dr. Manos said yesterday in her office at the Johns Hopkins School of Hygiene and Public Health, where she is a visiting scholar.
That same curiosity honed by years of scientific training has guided her to a discovery that has drawn international attention: a family of sexually transmitted viruses is responsible at least 93 percent of human cervical cancers worldwide.
Details of the finding, gleaned from 1,000 patients in 22 countries, were reported in yesterday's Journal of the National Cancer Institute. Dr. Manos performed an indispensable role, using a technique she developed at a California biotechnology company to search the tumors for genetic evidence of the so-called human papillomaviruses (HPV).
Quietly, scientists are hinting that when she further refines her technique, she may discover that the virus causes all of the half-million cases diagnosed around the world every year.
To Dr. Manos, 37, the finding means that cervical cancer can now be attacked as an infectious disease, fought with a vaccine that could subdue the virus before it has a chance to cause the cellular changes that progress to cancer.
"The fact that cervical cancer was a sexually transmitted disease has been suspected for a long time," said Dr. Phoebe Mounts, a Hopkins professor of molecular microbiology who has studied HPV extensively. "What was missing was this global study that looked at the role of the virus in countries around the world."
The project, co-directed by scientists from the World Health Organization, was a monumental feat of organization.
Doctors in places as diverse as Algeria, Mali, Germany, Thailand, Panama and the United States took specimens from their cervical cancer patients. They packed the samples in dry ice and shipped them to a WHO laboratory in France, which logged and forwarded them to Baltimore.
"They came in anything you can imagine," said Angela Jansen, a research technician who worked alongside Dr. Manos. "Little bottles, boxes, bags."
One hospital stuffed specimens into recycled bottles that had once held saline solution, then corked the spout.
"Considering the magnitude of the study, it's a miracle that all the specimens were in good shape."
Ms. Jansen described Dr. Manos as a strict but supportive mentor who engenders intense loyalty.
She also cited her quest for perfection in laboratory technique, drawing an analogy.
"Some people park their cars well, but some exactly between the white lines, I mean perfect. If you just park your car and it's not perfect, she'll tell you."
Despite her childhood foray into medicine, Dr. Manos chose the life of a research scientist while an undergraduate at the University of Arizona. It's a life of endless and often mind-numbing hours in the laboratory, examining specimen after specimen for clues to what makes diseases occur at their most basic level.
"What it was about the research people -- they were incredibly bright and very committed to what they were doing. And they were having fun doing science and answering questions," Dr. Manos said. From them, she adopted an outlook that she has tried to pass on to others.
"If you're not having fun, we need to talk about it and do something different," she said.
Dr. Manos obtained her doctorate in microbiology at the Cold Spring Harbor Laboratory, part of the State University of New York. She went on to direct the infectious disease section of the Cetus Corp., a biotech company near San Francisco where she worked for seven years before coming to Hopkins in 1993.
Cetus was the company that developed a revolutionary technology known as PCR -- polymerase chain reaction -- that enables scientists to study the genetic makeup of particles as vanishingly small as viruses. It's a technique that has unraveled important clues to the AIDS virus and helped police trace hair and blood samples gathered at crime scenes.
Using PCR, Dr. Manor developed the technique to accurately detect the human papillomavirus. She not only figured out how ** to find the genetic material in cervical secretions or a malignant tumor, but also to differentiate one type of HPV from more than 30 others in the family.
"It turned out that our method was at that time the most accurate method of looking for genital HPV infection," she said.
She used the technique in a study of 500 women at the Berkeley campus of the University of California, discovering that 40 percent of them carried the viruses. Medical histories revealed that the most sexually active women were most likely to be infected.
Later, she led a U.S. study that found the virus was much more common in women with cervical cancer than it was in noncancerous women. This showed that the virus was not only sexually transmitted, but it was associated with the second most common cancer in U.S. women.
In separate studies, scientists in Spain and Colombia made similar observations. But the study published yesterday was the first to establish that the virus causes the gynecological cancer in all regions of the world. Without that understanding, scientists would have no way of knowing if a vaccine would be a reasonable global strategy against the disease.
"She's a brilliant scientist who has an incredible grasp of the basic scientific and molecular biology, but she has what many scientists don't have," said Catherine Greer, a former colleague at Cetus who is now trying to develop an HPV vaccine at another firm.
"She has the ability to see the big picture -- what this means in public health."