Altering Cell Fate

HELEN BLAU says she has always been interested in the plasticity of cell fate. Twenty years ago, in a paper in Science, she reported that when various types of cells were fused with muscle cells, they could start expressing muscle genes. That finding challenged a widely held view that a terminally differentiated cell — a muscle cell, a blood cell — could never reach back and activate the untapped genetic potential of its embryonic days. In other words: Once a skin cell always a skin cell. Not necessarily, said Dr. Blau.

In the years since, Dr. Blau, Director of the Baxter Laboratory at Stanford University, has continued to explore cell plasticity. But she had never worked with stem cells until she was selected as a Senior Scholar by The Ellison Medical Foundation in 2001.

“The Ellison gave me the chance to get started,” she said. “Now most of my lab is devoted to this.”

Her Ellison-supported work, done in human cells and mice, found that bone marrow derived cells and hematopoietic stem cells can participate in a variety of tissues, expressing the genes found in those tissues. “We think it’s a kind of rescue mechanism that occurs in response to injury from exercise or toxins,” she said. She admits that the frequency of the phenomenon is very low, but says the same was true for cloning not so many years ago. “The question is now, what are the homing signals? How can we enhance a natural phenomenon? Why do some cells do it faster or better?”

In a field where political and scientific issues fuse like cells in a dish, Dr. Blau’s findings have placed her in the center of impassioned controversy. Some advocates of embryonic stem cell research – which has been limited by the federal government on ethical or religious grounds – have disputed Dr. Blau’s interpretations of her findings, arguing that they do not have the therapeutic potential of embryonic research.

“I think it’s not considered politically correct to work with adult stem cells because it’s thought this will hinder the cause of embryonic stem cells,” Dr. Blau said, adding that she opposes government limits on any stem cell research. Of her work, she said, “I’m not political about this – I’m following the biology.”

At the same time, she thinks people are moving too quickly to test adult stem cell transplants in humans before the long-term effects are clear. “I have people calling me up, saying ‘Please, treat my child, she’s dying,’ ” Dr. Blau said. “I can’t do that. I think we need to understand the science better.”

Dr. Blau was born in England and grew up in Germany and France. For an expert in plasticity, it seems fitting that she speaks French, German and English – both the American and British variants – without an accent. She says her interest in science began with curiosity about the physical world. It got a boost when she won a sixth grade science fair by identifying a skull she had found in the mountains. (It was a red deer doe.).

At 20, she was inspired about the possibilities of America by a summer she spent teaching Upward Bound in the Bronx. Doing graduate work at Harvard confirmed her feelings: “It was exciting that people could like you for your differences; in Europe you’re always trying to blend in. At Harvard you felt your limits were your own – if you had the energy and desire, you could do anything. In Europe it matters a lot what school you went to and who your parents are, your lineage.”

Another attraction, Dr. Blau said, was that Americans thought a woman could have a science career and still have children. She did both: She and her husband and two children, now grown, have traveled together to 23 countries, she said.

Like many scientists at her level, Dr. Blau says she no longer generates data in the lab because other lab members are better at it. But she says she loves her lab and the people in it. “I love to see original data,” she said. “I like to look down the microscope and see things other people haven’t seen.”

Dr. Helen M. Blau Ph.D.

Stanford University School of Medicine