Scientist, artist, teacher, pioneer

General Article

Liz Caldwell will retire this month after 30 years managing the center's Electron Microscopy resource that she built

Electron microscopist Liz Caldwell has collaborated with center researchers on projects that have led to numerous advances in cancer research. Caldwell retires at the end of this month after 30 years at Fred Hutchinson. Photo by Todd McNaught

On any given day during 30 years as manager of the Electron Microscopy shared resource, Liz Caldwell has never been sure what might show up on her lab bench. It might be a fruit fly with defective wings. Maybe a sample of cells infected with HIV. Or a bit of lung tissue from a marrow-transplant patient suffering from a hard-to-diagnose complication.

Whatever the specimen, Caldwell and members of her staff will go through the painstaking process of fixing and drying the tissue with chemicals, the essential first step of preparing a sample for viewing under electron microscope. They'll then embed the sample in molten plastic-like material, which will harden into a solid block. Next, they'll hover over a machine that looks like a miniature deli slicer, which will section the encased tissue into whisper-thin strips one one-thousandth of an inch thick.

"People think it's the most tedious kind of work you can imagine," Caldwell said. "And you don't know if you got it right until you get to the scope and take a look."

It's the look — the ability to see the inner workings of a cell or virus magnified 100,000 times — that has kept Caldwell on the edge of her seat and filled with wonder for the past three decades. She'll retire at the end of the month from a career that she describes as "the most exciting job I can think of."

"This has been the died-and-gone-to-heaven kind of job for an electron microscopist," she said. "Working at the center, I've looked at so many different things. Often I've been the very first person to ever see something. I've never been bored."

She also attributes her job satisfaction to fellow staff members Franque Remington, Judy Bousman and Bobbie Schneider, as well as longtime former colleague Judy Groombridge. Schneider will take over as manager in October. Collectively, the current Electron Microscopy (EM) staff members boast more than 100 years of experience.

Loves the field

Caldwell's endless enthusiasm is what has made her a superb collaborator and scientific resource, said Janell Baldwin, director of shared resources and Caldwell's colleague of nearly 15 years.

"Liz loves her field so much, she puts in the time to keep current on methods," she said. "That has allowed her to excel in her field. We have had people leave the center and continue to work with Liz to do their electron microscopy. She is a wonderful and patient teacher."

Caldwell's eagerness to guide a novice through the process of electron microscopy has been essential to many discoveries made at the center, said Dr. Robert Hackman, director of pathology and one of the first to tap Caldwell's skill.

"Liz was always willing to help out in any way she could and has always been eager to look closely at whatever someone was interested in," he said. "She just charges ahead. She and Judy (Groombridge) spent a lot of time with me on the scope, holding my hand through the process and opening their facility to our group."

One of the findings to emerge from the pathology group's electron microscopy experiments — which involved Drs. Betty Galluci, Howard Shulman and George Sale — was the visualization of immune-system cells in contact with and apparently attacking skin cells in patients with graft-vs.-host disease (GVHD). The condition is a major complication of bone-marrow and stem-cell transplantation.

"That point-to-point contact was something we had expected but hadn't been able to see before," Hackman said. "This helped in understanding the possible mechanisms of GVHD and was considered a breakthrough."

"A lot of the projects that we've chosen to follow up on in the laboratory have been things we learned from EM," said Dr. David Hockenbery, an investigator in the Clinical Research Division. "It's opened up some new directions for us. Liz's work has been very high quality and she's always very eager to try new procedures."

Caldwell also established a long-term research collaboration with a former Hockenbery lab postdoc who now works in Italy, an arrangement that Hockenbery said has been of tremendous benefit to both laboratories.

After graduating from college at the University of Washington, Caldwell took a pathology laboratory position at the UW in 1960, where she learned electron microscopy. Later, she held a position at the local veteran's affairs hospital. In 1974, a call came from Dr. Bill Hutchinson, the Seattle surgeon who was creating a new cancer center dedicated to his brother Fred. Caldwell's name had been given to Hutchinson by a doctor at Swedish Hospital who had learned electron microscopy from Caldwell.

"He was very direct," she said. "He asked, 'Could you come set up an EM facility at the cancer center?' I said, 'Yes, I think I can.' I almost told him that I'd come for nothing. It was my dream job."

Electron Microscopy was the center's first shared resource. During the three decades of her career at Fred Hutchinson, Caldwell watched the explosive growth of shared resources and the center as a whole.

"When we opened the doors to the new building in 1975, we had 165 people working here," she said. "I knew everybody, and it felt like a family. I'd talk to Hutch (Bill Hutchinson) every day, he was a wonderful man."

Improved technology

Although the center changed significantly over the years, the science of electron microscopy has not, Caldwell said. The instrument beams electrons across or through a biological sample, which is held inside a vacuum tube. Scanning electron microscopes allow the surface of a cell or other sample to be visualized in great detail, while transmission electron microscopes are used to examine thin cross sections of tissue.

"The theoretical resolution of what could be seen with the EM had already been reached by the time I started, and the optics were terrific," she said. "But vacuums and the mechanical systems were very poor back then. Two days a week the microscope would work, and the rest of time it was being repaired. Now, instruments have incredible vacuums and use solid-state technology. Everything is computer driven."

Today, the EM shared resource has one scanning microscope and two transmission microscopes, as well as four staff members.

"Liz is leaving the facility in great shape," Baldwin said. "We have excellent equipment and Liz has assembled a great staff."

An avid reader, Caldwell intends to spend much of her new found free time immersed in a good novel. She's also developed a knack for photography, a hobby that grew from the years she has spent on the job creating striking images of cells and microbes.

"Electron microscopy is as much art as science," she said. "It still blows me away how incredibly complex and beautiful the human body or a fruit fly or a virus can be."

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