Program pioneers a path for Frederick’s science

As the winter of 1973 turned to spring, the Frederick Cancer Research Center (FCRC), the forerunner to the Frederick National Laboratory and the National Cancer Institute (NCI) at Frederick that exist today, neared the one-year mark since its opening. The more than 250 employees had made sound progress, given the challenges of converting the old Fort Detrick biowarfare facilities into a fledgling cancer center.

Their efforts had drawn some attention, too. In January, NBC’s Tom Pettit and a film crew spent three days shooting footage and reporting on-site for the network’s First Tuesday program. Before that, in August 1972, Soviet Minister of Health Boris Vasilievich Petrovsky visited and toured the facility, much to President Richard Nixon’s apparent delight.

“Now he stood there, this man from the Soviet Union. This place has become a symbol of an open world, a world of cooperation and trust, at least in this particular area [that is, disease research],” Nixon later said of Petrovsky’s visit.

The National Cancer Advisory Board, a committee of 23 esteemed cancer experts appointed to counsel the NCI, also turned its attention toward FCRC. By early 1973, it had assembled an ad hoc subcommittee led by Sidney Weinhouse, Ph.D., director of the Fels Research Institute, to review the center and advise on improvements.

The Weinhouse Committee wasted no time. Its members visited FCRC in March and held two subsequent administrative meetings in Bethesda, Maryland, in March and June. They produced their report on June 20, just two days after their final meeting.

The verdict was favorable—but only in part.

A black-and-white photo of a flat building
Building 560 on the FCRC campus, photographed in the early 1970s. It was where many of FCRC’s laboratories and offices would be located in its first few years. Courtesy of the Office of NIH History and Stetten Museum

“With regard to the [FCRC’s] overall organizational framework, at its first meeting the Committee was favorably impressed by the speed and apparent efficiency of the changeover from a biological warfare center to a cancer research center. This was carried out with excellent forethought to comply with the spirit and the letter of the charge,” the report said.

However, it also said that FCRC lacked a clear overall aim and suffered from a lack of connection between its existing programs and support groups. The committee members admitted the situation could be left unaltered, but that wouldn’t do.

“The Committee feels strongly that such a limited goal would not fulfill the hopes and expectations of the National Cancer Board that this facility might become a world-renowned center of pioneering, innovative research in cancer,” they wrote.

They proposed an ambitious solution: bring a nationally or internationally renowned scientist to FCRC to establish and direct a large, semi-independent group that could spearhead the facility’s research. They further recommended that this new director be given a $2.5 million budget, enough to fund 10–20 lead scientists and between 80 and 100 additional staff.

After tense deliberations in November 1973, the National Cancer Advisory Board accepted the report and recommendations. The NCI agreed to execute it. The initiative that would soon become FCRC’s new Basic Research Program was cleared to begin.

By early 1974, the concept of the first investigator-initiated research program in Frederick was firmly approved. The idea had passed through the necessary channels, and the National Cancer Institute (NCI) and the Frederick Cancer Research Center (FCRC) set about making it a reality.

‘Dark Horse’ Becomes Director

FCRC published a press release advertising the position of program director on January 29, 1974. At the same time, NCI Director Frank Rauscher Jr., Ph.D., invited cancer researchers to submit their suggestions for candidates to Robert Stevenson, Ph.D., FCRC general manager and search committee chair.

Michael G. Hanna Jr., Ph.D., was a thirtysomething-year-old scientist and director of the Immunology of Carcinogenesis Group at Oak Ridge National Laboratory in Tennessee when he got a call about the job. He had heard of FCRC in passing and was only mildly aware of the search, but a colleague must have recommended him to the committee.

Four headshots of people in black-and-white
The leaders of the Basic Research program, pictured c.1974. Clockwise, from top-left: Dr. Michael G. Hanna Jr., Basic Research Program director; Dr. Margaret Kripke, head of the Immunobiology of Physical and Chemical Carcinogenesis Section; Dr. Isaiah “Josh” Fidler, head of the Biology of Cancer Metastasis Section; and Dr. James “Jim” Ihle, head of the Immunobiology of Viral Carcinogenesis Section. (FCRC Focus)

“They wanted to interview me,” he recalled. “Actually, they wanted to interview five people from Oak Ridge, and they asked all five of us to come up at the same time to be interviewed at the FCRC.”

The group boarded a plane and flew to Frederick, yet Hanna was sidelined soon after arriving. He developed severe gastritis from eating a bad oyster and had to be hospitalized. Frederick Memorial Hospital discharged him the following morning, but instead of traveling the few short blocks west to FCRC for his tour and interview, he headed southeast toward the airport, where he bought a ticket and flew back to Tennessee.

“I was sick, and I just wanted to get home,” he said.

Hanna felt that the mishap had cost him his shot at the position, but he made peace with it. He hadn’t been certain about the opportunity, anyway.

In July 1974, he got a surprise.

“I got another call from them, and they said, ‘We’re going to be … interviewing some people in New York, and we want to interview you. Would you come to New York?’” he said.

Serendipitously, he was preparing to travel to the United Kingdom for the Second International Congress on Immunology. The flight included a stopover at John F. Kennedy International Airport in Queens. Hanna remained ambivalent but decided to give the opportunity a chance, and the committee members agreed to meet him at his hotel and interview him before his flight overseas.

“I was very relaxed [in the interview] because I didn’t want [the position], I knew they weren’t going to want me, and I had to catch a plane,” he recalled, citing how he was a young scientist and an underdog candidate.

He received his second surprise after arriving at the airport and boarding the plane for the United Kingdom. An attendant presented him with a small bottle of champagne, compliments of the search committee, and said they wanted to offer him the job once he returned.

The offer occupied Hanna’s thoughts throughout the conference. He realized the magnitude of the scientific opportunity and the benefits that moving to Frederick, a less insulated community than Oak Ridge, would bring his family.

When he returned to the U.S. a few days later, he met with NCI Director Rauscher in Bethesda to discuss the position. Then he drove to FCRC for a tour and meetings with its staff.

He accepted the offer.

The Minds Gather

Hanna won out over a field of 80 candidates, but his selection veered from the Weinhouse Committee’s recommendation to recruit a widely renowned scientist. Few nationally acclaimed researchers were referred to the search committee. Hanna himself recognized that he wasn’t one of them, as did Rauscher, the committee, and others.

A black-and-white photo showing two scientists stand in front of a chalkboard
Dr. Michael Yarmolinsky (left) and Dr. Robert Yuan (right) work at a chalkboard. Both were senior scientists in the Cancer Biology Program. Photo likely taken in 1980. 1980 annual report

Instead, the committee reported seeing in him “a younger scientist of demonstrated ability and likelihood of future growth, with a clear concept of purpose and an imaginative program.” His recruitment apparently was a chance to bring a fresh scientific perspective to the young FCRC, and his proposed interdisciplinary program—cancer immunobiology—seemed promising.

“[He is] a bright young man who can attract the kind of people we need to develop a first rate [sic] program at Frederick,” Rauscher said at the time.

The claim proved to be true. By the time news of the selection broke, three other promising young scientists had already accepted Hanna’s invitations to lead new sections in the Basic Research Program.

All three were warm colleagues with Hanna and shared the hope of doing meaningful research at Frederick. Margaret Kripke, Ph.D., came from an assistant professorship at University of Utah. Isaiah “Josh” Fidler, D.V.M., Ph.D., left a tenured associate professorship at University of Pennsylvania to join the program. James Ihle, Ph.D., like Hanna, moved to Frederick from Oak Ridge National Laboratory.

“For me, it was an opportunity, a real growth opportunity, because it was leadership experience. It was starting a new laboratory from scratch. It was being part of an exciting, growing program, and there was a lot of enthusiasm and a lot of energy around the science,” Kripke recalled.

Kripke and Fidler had reason to be doubly excited. They wanted to marry and had been looking for an institution to which they could move together. When Hanna contacted them separately to offer leadership roles in the new program, everything clicked.

“[Accepting] seemed like the right thing to do,” said Kripke, who married Fidler in Frederick.

Hanna consulted part-time with Litton Bionetics, FCRC’s contractor, while FCRC prepared for the program during the final months of 1974. Construction crews began renovating Building 539 to accommodate the new laboratories.

Then, early in 1975, the eagerly awaited day arrived. The Basic Research Program officially began operating.

Unsurprisingly, the new Basic Research Program at the Frederick Cancer Research Center (FCRC) took some time to gain momentum despite the preparations that had been made.

Margaret Kripke, Ph.D., head of the program’s Immunobiology of Physical and Chemical Carcinogenesis Section at the time, recalls that her first year was dedicated to setting up her new laboratory, hiring staff, moving around, and finishing projects she had started in her former laboratory at University of Utah.

“When I got there, my laboratory had a large hole in the exterior wall, and that was where they were bringing in all the equipment, so it took quite a while,” she recalled. “I was in borrowed space until then or I was in a very small space until they finished.”

But the program quickly hit its stride. Michael G. Hanna Jr., Ph.D., the program’s director, had come from Oak Ridge National Laboratory and didn’t view FCRC as just a government contract. To him, it was a budding national laboratory in all but name, and he led the program with that perspective.

The staff’s enthusiasm, vision, and expertise intertwined. They soon began making important advances, and the program became the flagship scientific enterprise that the National Cancer Institute and National Cancer Advisory Board hoped it would be.

A black-and-white group photo taken inside a building
Senior staff of the Cancer Biology Program (formerly the Basic Research Program) in 1981, after Dr. Margaret Kripke became director. Back row, from left: Richard Roblin, Warwick Morrison, Mark Pearson, Thomas Silhavy, Robert Yuan, Michael Yarmolinsky, and Stuart Austin. Front row, from left: Nat Sternberg, Margaret Kripke, and Corazon Bucana. 1981 annual report

Advances Accumulate

Kripke and her laboratory continued her groundbreaking research from earlier in her career that had uncovered ultraviolet radiation’s ability to alter the immune system’s response to tumors and pathogens. This revealed a mechanism contributing to the development of skin cancers and some infectious diseases. She was especially prolific while in Frederick, authoring or co-authoring more than 50 publications in eight years.

Several of Kripke’s projects investigated ultraviolet wavelengths’ effects on melanoma development. FCRC even custom-built a machine that allowed her to do fractionated wavelength studies in the laboratory. Her work advanced the scientific community’s understanding and underpinned the eventual development of certain sunscreens.

Black-and-white photo
An unknown Cancer Biology Program employee pipettes liquid inside a biosafety cabinet, likely in 1980. 1980 annual report

Isaiah “Josh” Fidler, D.V.M., Ph.D., head of the Biology of Cancer Metastasis Section, and Kripke performed a landmark cloning study in 1977. Together, the husband-and-wife duo proved, for the first time, that tumors are composed of many different types of cells instead of identical cells, which opposed the prevailing theory at the time. The scientific and medical communities were slow to accept the findings, but the study has since been hailed as a milestone in cancer research.

James Ihle, Ph.D., head scientist in a viral carcinogenesis group, and colleagues in Frederick discovered interleukin-3, a naturally occurring protein that increases the number of cells produced by bone marrow. Their findings were published in 1981. Interleukin-3 is now used to boost the immune system in cancer therapy.

Around the same time, Fidler and a postdoctoral fellow, Ian Hart, Ph.D., demonstrated that cancer cells metastasize to new organs based on the cells’ predisposition independently of blood flow. The work validated Stephen Paget’s “seed and soil” theory of cancer metastasis that had gone unproven for 90 years. (By this point, Fidler’s laboratory had separated from the program into a standalone entity, but it remained an “offshoot” and continued to work closely with program staff.)

Meanwhile, Hanna and his laboratory were investigating the Bacillus Calmette-Guérin tuberculosis vaccine as a cancer treatment. Throughout the late 1970s and early 1980s, they published several studies demonstrating that the vaccine, combined with other treatments, could shrink certain tumors, eliminate metastases, and improve survival in guinea pig models of cancer. This laid the foundation for future studies that led to the FDA’s eventual approval of the vaccine to treat carcinoma in situ bladder cancer, for which it remains a primary and highly effective therapy.

The new environment with investigator-initiated basic research also led to FCRC’s first-ever programmatic peer review. A committee of well-respected scientists evaluated the facility, resulting in adjustments and—unfortunately—the closure of two programs. For groups that were doing well, like the Basic Research Program, it was a vindication. For those that were struggling, it proved an important opportunity to regroup, reorganize, and redirect efforts to be more effective.

“Then things started to really roll,” Hanna said.

The Basic Research Program saw major accomplishments outside the laboratories, too. Its staff helped organize conferences and hosted lectures that brought respected scientists to FCRC. These events called the scientific community’s attention to the small facility, which “was not on the beaten path for much of anything in those days,” Kripke said. Combined with the early scientific discoveries, they helped put FCRC on the map.

Other actions cultivated FCRC’s budding reputation. Basic Research Program staff frequently traveled to conferences to share their research. Kripke was named a U.S. delegate to the United Nations Environment Programme’s 1977 meeting on the ozone layer due to her expertise in ultraviolet radiation. Fidler was a leading voice in the metastasis field. Hanna; FCRC scientist Nat Sternberg, Ph.D.; and other staff collaborated with the U.S. Army Medical Research Institute of Infectious Diseases, Hood College, and Frederick Community College to educate the public about local research efforts by organizing a lecture series, Science in Frederick.

“Everybody [in the program] was excited about what they were doing, and everybody was able to do a lot of research,” Kripke said. “We did enormous numbers of experiments and things that probably couldn’t be done anywhere else.”

A black-and-white photo of two scientists working
Staff in the Cancer Biology Program performed a variety of independent cancer studies. Photo likely taken in 1980. 1980 annual report

A Good Place to Be

Like much of FCRC, the Basic Research Program enjoyed a strong sense of camaraderie in its early years. Hanna and Kripke recall it being a small, tight-knit group with a commitment to teamwork.

“Everybody had kind of different scientific backgrounds, and so it was very exciting. We learned a lot from each other,” Kripke said.

The collaborative spirit continued as the Basic Research Program grew, separated, and changed. New groups were established internally as time passed. Then, in 1979, Hanna was promoted to FCRC director, and Kripke became the new director of the program, renamed the Cancer Biology Program, shortly thereafter. Hanna’s and Fidler’s laboratories were reorganized into a separate program, the Cancer Metastasis and Treatment Laboratory, headed by Fidler. Despite the changes, the groups inside and outside the Cancer Biology Program continued to work closely. Frederick’s science was flourishing.

Kripke strived to foster strong relationships as the program’s new director. One of her first acts was to host a series of “pizza and beer sessions” for young scientists in the evenings. Program leaders would meet with these junior staff in an informal setting to hear about their scientific interests and determine ways to help them.

It was an enjoyable time to be part of the program, as evidenced by fond memories former employees have shared over the years. In a 2005 article for Cancer Biology & Therapy, Fidler wrote that those days in Frederick were “thrilling” and “rewarding” and that each “was more exciting than the preceding one.”

On Solid Ground

As the 1980s unfolded, the young scientists who had started the program decided to take the next step in their careers. Hanna transferred to the Litton Institute of Applied Biotechnology, a new research facility in Shady Grove, Maryland, in 1983. That year, Kripke and Fidler moved to Houston, where they became chairs of departments at MD Anderson Cancer Center. Ihle left FCRC in 1984 to join St. Jude Children’s Research Hospital, where he continued his work on interleukins.

A black-and-white photo of a man looking down between containers
A Cancer Biology Program employee handles a rack of containers, likely in 1980. 1980 annual report

The old guard’s departure helped mark a new period in the program, but the laboratories’ tradition of success would continue. Where the Weinhouse Committee had identified lagging independent research at the facility a decade earlier, there was now a thriving collective of laboratories and groups leading studies into cancer and other diseases.

It was the germ of the facility’s journey to becoming the National Cancer Institute at Frederick and the Frederick National Laboratory for Cancer Research, the scientific heavyweights that they are today.

“We ploughed those acres,” Hanna said. “It started out as a national laboratory—‘disguised’—and it ended up as a national laboratory for real.”

By Samuel Lopez, staff writer

In memory of Dr. Isaiah Fidler, 1936–2020.