Creager catches the bug for history of science

Steven Schultz

Princeton NJ -- As a graduate student in biochemistry, Angela Creager worked at the forefront of her field -- studying with top people and applying the latest techniques to the most current questions.

After earning her Ph.D. in biochemistry, Angela Creager won a National Science Foundation fellowship to learn a new discipline. Now an associate professor of history at Princeton, she teaches classes on the history of science and has just published her first book.

By the time she received her Ph.D., however, Creager was more interested in problems that had long since been solved and techniques that nobody had used in decades.

It was not a fall from grace -- just a change in career. Creager, now associate professor of history at Princeton, studies the history of biology. She has just published her first book, the story of how a seemingly obscure tobacco virus played a pivotal role in the birth of molecular biology.

"I tell people I'm an expert in obsolete knowledge," she said. "But I don't mean to trivialize it; it really is fascinating. And it helps you be more humble about current knowledge and its claims about being the final truth."

So while her colleagues in labs push forward the boundary of scientific knowledge, Creager works to establish where those boundaries used to be and to understand the cultural and scientific forces that helped propel people past them. In many ways, however, the pursuits offer some of the same rewards.

"When you do historical research, just like in a lab, you can be surprised by your findings," she said. "I love that about history. I love that you can be surprised."

Creager found plenty of unexpected facts and ideas in researching her book "The Life of a Virus," which was published last month by the University of Chicago Press. The tobacco mosaic virus, which commonly attacks tobacco plants but is harmless to people, was the first infectious agent to be recognized as something distinct from bacteria. After that discovery in 1898, viruses became the subject of intensive research. Creager shows how the tobacco mosaic virus, in particular, went on to play a leading role in areas from cancer and polio research to the development of modern laboratory equipment to the birth of genetics and biotechnology.

Even in the early part of the century, scientists believed that understanding viruses, which were too small to be seen with even the most powerful microscopes of the time, would lead beyond just fighting disease to understanding the origin of life itself. In 1935, biochemist Wendell Stanley created purified crystals of the tobacco mosaic virus, isolating it into a form that could be seen and studied.

"The idea that a virus -- something that reproduces itself -- could be as simple molecularly as table salt really grabbed people's attention," said Creager. "It came out on the front page of The New York Times the day the scientific paper was published."

Rethinking a legend

Following World War II, scientists adopted the tobacco mosaic virus as a model system for learning about viruses and genetics in general. One reason was that government agencies, which had seen the benefit of funding basic research during the war, turned their resources toward fighting a civilian war against disease.

Creager also reveals a less obvious force behind this development. Voluntary health organizations, such as the National Foundation for Infantile Paralysis (now known as the March of Dimes), were eager to fund basic research that would defeat polio and other diseases. Having been stung by disastrous early attempts at creating a polio vaccine, the private funders wanted to learn more about the basic biology of viruses before trying to develop more vaccines. One of their chosen research subjects was the tobacco mosaic virus, which was clearly harmless to people and was the best-studied virus available.

This story, noted Creager, ultimately undercuts the nearly legendary tale about the origin of molecular biology, which holds that physicists -- some disenchanted after the bomb -- turned to biology and solved the key problems.

The usual tale is that "they went into biology with their methods and their math and their reductionism and solved the secrets of life. It's a very attractive story in many respects and there are some very prominent molecular biologists who were previously physicists, but that's not the sole reason molecular biology was born," said Creager. "There was a tremendous impetus from the side of trying to fight disease and fostering basic biomedical research."

Ultimately, much of biology followed the idea of using model organisms, such as mice, fruit flies and E. coli, to answer key questions about life in general. "We know what we know about the world because we have chosen very specific objects and studied them to death. And tobacco mosaic virus is one of those objects," said Creager. "When you think about the number of person-hours that have been invested to understand just this one virus, it is incredible."

Today, the tobacco mosaic virus continues to play an important role in biotechnology, where it is used as a vehicle for transporting foreign genes into plants to create genetically modified crops.

Creager's interest in the tobacco mosaic virus dates back to her time in graduate school at the University of California-Berkeley. Although she did not conduct research on the virus, the building in which she worked was called Stanley Hall after the scientist who purified the virus and who founded Berkeley's department of biochemistry.

Throughout her graduate work, Creager was interested in finding connections between science and humanities, but did not have a clear idea of how to put them together. "Then I took this history of biology class and thought 'That's what I want to do!'" she said. "But at that point, I was only a year from finishing my Ph.D in biochemistry."

So instead of seeking conventional postdoctoral fellowships in science, she applied for a National Science Foundation fellowship in the history of science at Harvard. "I argued to the NSF that I needed to retrain completely, go to the graduate seminars and learn a new discipline," she said. "And, much to my surprise, I got the fellowship."

Three years later, in 1994, Creager came to Princeton as an assistant professor of history. She regularly teaches a lecture course on the history of biology and has co-taught a seminar with history department colleague Michael Mahoney on "computers and organisms."

Now with "The Life of a Virus" finished, Creager is starting a new project to study the role of radioisotopes in biology. Supported by another NSF grant, Creager is looking at how the U.S. government, trying to show civilian benefits of nuclear weapons research in World War II, provided radioisotopes to biomedical scientists. Isotopes then became a critical tool for tracking the progress of molecules through organisms.

As in her previous work, Creager said, the thrill is in finding the unexpected links between diverse details of a big picture. "How is it that this one particular thing is tied into so many much larger issues?" she asked. "It's very much about finding connections."