Fall 2000

A Legacy of Life

Considered one of the most important advances in cancer treatment, the Hutchinson Center's pioneering marrow-transplantation research has saved thousands of lives

by Barbara Berg

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A doctor, nurse and laboratory technician carefully lower a terminally ill leukemia patient into an underground bunker, carrying his stretcher down dark flights of stairs.

A former military facility in West Seattle, this makeshift "hospital" houses two cobalt-60 radiation sources, capable of firing a punch of radiation with biological effects as severe as those of an atomic-bomb blast. The potent rays—invisible to the eye—are unleashed on the patient, designed to destroy his bone marrow, devastating his immune system.

The group is led by Dr. E. Donnall Thomas, a well-known specialist in blood disorders. Deemed renegades of their profession by some in the medical community, the team is waging a war on leukemia.

The year is 1968, and bone marrow transplantation is considered an experimental procedure that brings patients to the brink of death with massive doses of radiation to destroy diseased marrow and then brings them back to life with transfusion of a new blood and immune system. The technique, first attempted in the 1950s, is intended to save the lives of leukemia patients with no other options—except death.

Following irradiation in the bunker, the patient is rushed back to an eight-bed transplantation ward at the U.S. Public Health Service Hospital in Seattle for a transfusion of donated marrow.

The medical team has hints that transplantation could improve the survival odds of desperately ill patients. Sporadic success stories from Thomas and others involving transplants with identical twins convince the team to keep at it—despite the skepticism of their colleagues.

Eventually, all doubts are erased with the team's courageous efforts. Today, bone marrow transplants are a proven success for treating leukemia and other cancers as well as blood disorders such as aplastic anemia. A diagnosis of leukemia was once considered a death sentence. Now, some leukemias have cure rates of 70, 80 and 90 percent.

The success of bone marrow transplantation to treat leukemia and other diseases of the blood is considered one of the most important advances in cancer treatment during the last quarter century. This advance is due largely to the perseverance of Thomas and his pioneering team, which, combined with the vision of Seattle surgeon Dr. William Hutchinson, gave rise to the Fred Hutchinson Cancer Research Center in 1975.

A world leader in transplantation biology, the Hutchinson Center has saved thousands of lives and trained hundreds of scientists who bring their expertise to institutions around the world. From humble beginnings, a world-class cancer research center was born.

The original Seattle transplant team's arduous attempts to save gravely ill patients fostered a closely knit group that paid no mind to rank or status of its members. A look back at the early days by some of the original participants—doctors, nurses, and research and support staff—reveals an unusual spirit of commitment to what was an uncertain goal.

"We moved to Seattle in 1963 at a time when it seemed that marrow transplantation would never be successful," Thomas recalls. "So we focused our attention on laboratory experiments."

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As chief of medicine at the Mary Imogene Bassett Hospital in Cooperstown, N.Y., Thomas began studies of marrow grafts, treating relatively few human patients. After moving to Seattle, Thomas and his colleagues worked almost exclusively in the laboratory well into 1967, postponing work on patients until treatment complications could be resolved.

Bone marrow is a spongy mass of cells that lines long bone cavities and houses the seeds that grow the entire blood and immune system. Because bone marrow gives rise to the immune system, marrow transplants are beset by a peculiar problem-donor marrow has the ability to identify and reject the transplant recipient's body as foreign, resulting in a condition known as graft-vs.-host disease (GVHD). Its effects can be devastating, including severe skin rashes and destruction of the digestive tract lining.

Transplants between identical twins, who share identical tissue types, escape GVHD, but allogeneic transplants—those between non-twin siblings—rely on careful tissue-type matching. As Thomas and colleagues began their studies, methods for typing human tissue were newly defined.

In addition to the problem of GVHD, the first step of the transplant procedure-destroying the marrow with radiation-temporarily leaves patients without an immune system to fight infection. So-called opportunistic infections can be managed today with a battery of drugs, but many early transplant patients died of such complications.

Reginald Clift
Convinced these problems could be overcome, Thomas joined the University of Washington's department of medicine and quickly attracted colleagues from around the world. In addition to Thomas' wife, Dottie, trained as a medical technologist and an integral team member, the first to join included Drs. Bob Epstein and Dean Buckner as well as technician Ted Graham, who had moved with the Thomases from Cooperstown.

With limited space at the university, the team set up shop in a few remodeled floors of the aging U.S. Public Health Hospital. Lacking radiation facilities in the hospital, patients were irradiated in the West Seattle bunker.

"Medicine was quite primitive in those days," Dr. Rainer Storb remembers. Storb, now head of the Hutchinson Center's transplantation biology program, left a position in Paris in 1965 to join Thomas in Seattle and recalls his first glimpse of the facilities. "I was quite surprised by the physical setup, especially after coming from Germany where hospitals were very modern."

Judy Campbell, one of the first nurses Thomas hired to care for the transplant patients, agrees that the public health hospital was indeed dismal. "Mustard yellow walls, brown floors—before we moved out to new facilities we allowed patients to have some fun by decorating and painting their walls."

But the challenges of the physical surroundings were nothing compared to the obstacles of the transplant procedure itself. The first patient who received an allogeneic graft after careful tissue typing of siblings died of complications from an infection. Protecting future patients from attack by infectious agents was the first big challenge.

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Reginald Clift, who left a medical post in Africa as a member of the British Colonial service to join Thomas, teamed up with Buckner to redesign patient rooms in order to achieve a germ-free environment. Patient isolation and laminar airflow systems, scrupulously efficient filters, were tried.

"The idea was to have a sterile environment," Clift says. "We did studies of sterile food-some of which was totally inedible." Thomas hired nutritionist Saundra Aker to experiment with sterile food, which was put in an autoclave, a large pressure cooker used to sterilize laboratory utensils.

"At that time everybody had to wear a mask when they went into the patient rooms," Dottie Thomas says. To cheer up patients, who saw only masked visitors, the nurses stopped wearing uniforms and challenged each other to wear the most colorful outfits. "Everyone wanted to wear bright, flowery things. I think it made a big difference to the patients."

Today, improved antibiotics eliminate the need for sterile rooms and food, giving patients more normal contact with visitors and medical staff.

In 1968, additional expertise joined the effort with the arrival of Drs. Alex Fefer and Paul Neiman, both researchers from the National Cancer Institute. Fefer was an immunologist who had discovered that certain types of white blood cells-immune-system cells-had the ability to recognize and fight leukemia cells. Subsequent work by the Seattle team extended these findings to discover the "graft-vs.-leukemia" effect, which occurs when donated marrow cells actually attack residual cancerous cells in the patient that have not been completely eliminated by radiation.

Neiman had been trained in medical oncology, a relatively new field at the time.

"I brought experience in managing patients with chemotherapy," says Neiman, who went on to found the Basic Sciences Division of the Hutchinson Center. "I also had some training in molecular biology. I think Don thought it would be great to have somebody on the team who had a foot in that camp."

As the team grew, overcoming the severe effects of GVHD was the next challenge. One of the first breakthroughs came with the discovery of the immunosuppressant anti-thymocyte globulin (ATG), which Storb collected himself from horse serum from animals on a Redmond farm.

ATG's ability to alleviate GVHD was first tested on Tamara Stevens in 1972, then a 16-year-old girl (see story on page 6). Her parents, told that the treatment was still highly experimental, agreed to take the chance in order to save their daughter, who is still alive today.

"She responded unbelievably well," remembers Storb. "In those days, patient consent meant that you sat down with the family and discussed things. The doctor-patient relationship was very important."

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Slowly, each year the number of patients transplanted grew as each obstacle was tackled. The team, and the world, would not be certain of the long-term success of their efforts until their 1977 paper was completed, Cure of Leukemia by Marrow Transplantation. The paper was a follow-up of 110 patients transplant patients that reported a 16 percent long-term survival.

Until marrow transplantation was an accepted practice, the Thomas team encountered criticism from some who felt the procedure would never work.

Dr. Don Thomas and Dr. Otto Sahler
Dr. Don Thomas, standing, started his marrow-transplantation research as chief of medicine at Mary Imogene Bassett Hospital in Cooperstown, N.Y., before moving to Seattle in 1963. Thomas and Dr. Otto Sahler are pictured here with an early radiation machine. Hutchinson Center Archives
"In the 1960s in particular and even into the 1970s, there were very responsible physicians who said this would never work," Thomas says. "Some suggested it shouldn't go on as an experimental thing."

"It was an unbelievably insecure time," remembers Fefer.

Campbell, the transplant-ward nurse, recalls that despite the criticisms the team's commitment to curing cancer never wavered. "We kept on going, using what we had to give the best possible care."

The early success was enough to convince Dr. Bill Hutchinson to support Thomas and his team and build the group a permanent home. In 1972, ground broke for the construction of the original Hutchinson Center building in Seattle's First Hill neighborhood, and its doors opened in 1975.

Expansion of the Hutchinson Center spawned a basic research arm and an epidemiology program to augment the clinical research. Today, more than 2,500 staff carry out the Hutchinson Center's mission to eliminate cancer as a cause of human suffering and death.

"One of the great things about the Hutch is that there has been an emphasis on quality up and down the line—which is why from its start in 1975, the Hutch has become an international figure in cancer research," Thomas says. "It carries on."

Barbara Berg, Ph.D., is a science writer for the Fred Hutchinson Cancer Research Center.


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