Impact of Thomas's Work

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Impact of Dr. E. Donnall Thomas's Work

Dr. E. Donnall Thomas and his wife Dottie with former patients and their families at a Hutchinson Center Patient Reunion.

It was 3:40 a.m., a Monday morning in the fall of 1990, when an East Coast reporter called Dr. E. Donnall Thomas with the news:

He and Dr. Joseph Murray, a longtime friend and pioneer in the field of kidney transplantation, would share one of the world's most prestigious honor

"At first I thought there was something wrong at the hospital, but then he was saying something about it just being announced -- I had won the Nobel Prize," says Thomas, whose four decades of bone marrow transplantation research was recognized by the award.

"I thought someone might be playing a trick, but when he told me the co-winner was Joe Murray, it started to make sense. So I sat there for about five minutes explaining marrow transplants to the reporter."

Thomas' wife and life-long research partner, Dottie, was perplexed by the early wake-up.

"She asked me why was I giving an interview at 4 in the morning," Thomas recalls. "And I said, 'Well, it looks like we won the Nobel Prize.' And she rolled over and went back to sleep."

Moments later, Dottie Thomas' eyes popped open. "WHAT did you say?"

"The Nobel Prize," Thomas said.

Thomas' use of the word "we" was deliberate. Although Dottie Thomas' name did not appear on the 1990 Nobel Prize awarded to her husband and Murray in Stockholm, she and his many colleagues and patients in research "made this happen," he says. "Many people did this. It was not a single effort."

In recognition of that fact, the Thomases donated the $350,000 Nobel Prize award to Fred Hutch.

Early marrow transplantation research

Don Thomas and the former Dottie Martin met at the University of Texas at Austin in 1939, where he began his studies in science and she pursued journalism courses. After their marriage, Thomas went on to medical school at Harvard University. It was in medical school that Thomas became interested in bone marrow and leukemia, an interest he readily shared with his wife.

"We realized early on that if we were ever going to see each other she needed to get into medicine or some field of science," Thomas says. "She gave up her journalism studies for this."

Dottie Thomas entered training through New England Deaconess Hospital, determined to become a medical technologist.

The two have worked side-by-side in the lab and in the office ever since. From their early work at the Massachusetts Institute of Technology, trying to determine factors that stimulate marrow function, to dog and human marrow transplantation studies conducted at Mary Imogene Basset Hospital in Cooperstown, New York, the Thomases have been a single and dedicated unit.

The New York research quickly showed Thomas and his colleagues that allogeneic transplant — that is, transplants between non-twin siblings — would be difficult to achieve.

"There were a lot of problems we had to work out," Thomas says. "Back then, we didn't know anything about histocompatibility (tissue typing)." Since the 1960s, researchers have discovered that tissue typing, not just blood typing, is vital to any successful transplant.

Brilliant minds meet in Seattle

The Thomases moved to Seattle in 1963 at the invitation of Dr. Robert Williams, first chairman of the University of Washington Department of Medicine.

They and fellow researcher Ted Graham took up residence at the Seattle Public Health Service Hospital and the "rest of the story seems short in retrospect," Thomas said in a forward to his Nobel Lecture.

His belief that transplantation eventually would save lives led to "the recruitment of some brilliant young co-workers who still work with me, studies of immunology and irradiation biology in dogs, borrowing knowledge of histocompatibility from other research efforts, the assembly and training of a critical care team of nurses and, finally, the demonstration that some patients with advanced leukemia, aplastic anemia or genetic diseases could be cured by marrow transplantation," Thomas wrote in his 1990 address.

When then — President Richard Nixon threatened to close the public health hospital in 1972, Thomas secured a $250,000 grant to move his dog and human marrow transplant research program to Providence Hospital. The University of Washington had no room for his growing endeavor at the time.

In 1975, the research team transferred to the recently formed Fred Hutch's new structure on First Hill, now called the Columbia Building, making bone marrow transplantation the central focus of the center's clinical research division.

Through the center's history, that focus has not changed, and center doctors now perform about 450 transplants a year and participate in 100 more in Northwest community hospitals.

Steps on the road to a cancer cure

It's difficult to whittle the couple's two plus decades of research into a few choice highlights, both Dottie and Don Thomas say. In each lab and experimental success, scientists have unraveled a piece of the cancer puzzle. No one piece stands alone.

But the Thomases point to several markers on the road to understanding and perfecting bone marrow transplantation as a means of cancer treatment.

In the 1960s, their attention was centered on dog experiments, learning about the immunology and irradiation biology of these outbred animals suitable for clinical care comparisons to human patients.

During that decade, Thomas and his colleagues mapped the ins and outs of dog tissue typing and continued to perform twin bone marrow transplants. Identical twins, with identical genes, were used, creating a perfect tissue and blood match, although doctors found other complications post-transplant, the main one being that cancer recurred in many patients.

By applying their own research and studying research conducted in the United States and Europe, they came to understand much about human tissue typing.

The advance of knowledge about histocompatibility and improved techniques to compare tissues is a major improvement in the field of transplant research, Thomas says.

Another important advance was the development of second- and third-generation antibiotics for controlling bacterial infections in patients, he says. Today, some 40 different diseases are treated with bone marrow transplantation, a far cry from the days when leukemia and aplastic anemia patients were the only recipients of the treatment.

The first successful non-twin, or allogeneic, transplants between siblings occurred in 1968 and 1969. Autologous transplants were performed in the 1970s, but such transplants were soon discontinued while researchers worked out the many problems of the procedure.

Finally, in 1979, Laura Graves became the first Hutch patient to receive marrow from an unrelated marrow donor to treat her leukemia, a success that led to development of the national marrow donor registry. Today, international registries allow donors in one country to save lives in other countries.

Autologous transplants are now conducted outside the Hutch in community hospitals.

From bunkers to the Hutchinson Center

Technology in the lab and clinic has noticeably changed in recent years, Thomas says. Ten years of research on dogs conducted before the Hutch opened "could probably be accomplished in six months with today's technology," he says.

Before the doors of the center opened, Thomas and his fellow researchers had to travel to a World War II bunker in order to carry out their irradiation experiments in dogs. Several human transplant patients also had to be transported to a dog irradiation center in West Seattle for the therapy before they were transferred back to the Public Health Services Hospital for the transplant procedure.

"In 1969, the dog facility was the only place where we could do total body irradiation. We went back and forth between facilities like ping-pong balls," Thomas says.

"When the Hutch opened, it was the first time we had good facilities, with everything in one place. It made an amazing difference."

An ongoing commitment to fight cancer

The Thomases' three children, Don Jr., Elaine and Jeffrey, have been all but raised at the Hutch. At one point, all three children worked at the center alongside their parents.

Don and Elaine are now physicians and researchers in their own right, and Jeffrey is a successful businessman. At the Thomas dinner table, the center was always a central topic.

"Our daughter was 12 years old before she realized not everyone's parents worked every weekend," Dottie Thomas says with a chuckle. "Elaine practically grew up in this place."

Although Don and Dottie Thomas are technically retired, neither sees a future far from the center. They continue to work side-by-side in their office on the fifth floor of the Thomas Building, named for Don and opened in 1998, helping raise money for and awareness of the center's fight against cancer.

"Dottie says that now that we're retired, we can cut back to seven days a week," Thomas says. "She's working just as hard as ever. I asked her recently if she was enjoying her retirement, and she just about hit me."

"We love what we do," Dottie Thomas says. "I can't imagine working or living any other way."

What's the secret to their long partnership and marriage?

A single grin passes over both faces.

"I'm so easy to get along with," they say in unison.

Dr. E. Donnall Thomas, recognized as the father of bone marrow transplantation, died on Saturday, October 20, 2012, at the age of 92. Learn more about his life and work and share your remembrances.