How a phone call helped shape the field of bone marrow transplant

A lifesaving new leukemia treatment was harming some patients’ digestive organs, and no one really understood why. So, over 40 years, Dr. George McDonald helped fill in the gaps.
Dr. George McDonald
Dr. George McDonald Photo by Robert Hood / Fred Hutch News Service

It was August 1972, and Dr. George McDonald was mystified.

Just two months into his fellowship, the young physician was fielding consultation requests for patients with gastrointestinal and liver problems. But the phone call from Dr. Don Thomas was different. The future Nobel Prize winner, whom he’d never met, had mentioned bone marrow transplantation and a sick patient and something called "graft-vs.-host disease." Could McDonald come do a consult?

Of course, he replied. Then he hung up the phone.

“I had no clue what he was talking about,” McDonald recalled.

He raced to the library to consult the massive Index Medicus — “the paper-based Google of its day” — and looked up GVHD and bone marrow transplantation. It contained virtually nothing. And it contained even less about GVHD’s impact on the digestive system. 

Today, a similar search on the modern-day Google spits out an ocean of information. That’s in no small part thanks to McDonald. Over the past 40-plus years, he has helped the field fill in the blanks he found in 1972. First as an intrigued volunteer, then on the faculty of Fred Hutchinson Cancer Research Center, McDonald has helped unravel countless mysteries surrounding GI and liver problems in patients with cancer.

His contributions to the field — and Fred Hutch — are staggering, said Executive Vice President and Deputy Director Dr. Fred Appelbaum.

"Bone marrow transplantation is in our blood, and Don Thomas' work showed us how we could develop an idea from nothing but a concept into a therapy that would eventually cure thousands of people," Appelbaum said. "But that took a village. George was an incredibly important part of that village. Without him, we might not have gotten to where we are."

Exploring the unknown

Looking back, McDonald says Thomas’ patient probably didn’t have GVHD. But he was fascinated. Here was a chance to investigate diseases that hadn’t been fully researched or even described in the medical literature.

“You don’t want to go into a field where everybody knows everything already,” he said. “I thought these were the fields with the greatest need for deeper science.”

McDonald with visiting scientist Simone Strasser circa 1996 Photo courtesy of Fred Hutch Arnold Library

In 1972, bone marrow transplantation was still in its infancy. Thomas’ team had transplanted its first patient just three years prior. The procedure used radiation and chemotherapy to destroy a patient’s diseased bone marrow, then replaced it with new marrow from a healthy patient. The goal was to wipe out cancer and establish a new immune system.

But that goal often seemed elusive when McDonald picked up the phone. The very first transplant patients all had advanced leukemia, and cure rates in the early 1970s were grim. Most patients died from the toxicity of the transplant procedure, or infection, or GVHD, or recurrent cancer.

Crises could break out in nearly every major organ system in a transplant patient’s body. In response, Thomas and his team recruited experts from a wide range of specialties, all focused on marrow transplant patients. McDonald became their go-to gastroenterologist.

Dr. Rainer Storb, who pioneered transplant with Thomas and is one of the founding scientists of Fred Hutch, recalled McDonald as an eager member of that miniature school of medicine.

“He got really interested in the mechanics of what was happening to our patients,” Storb said. “George had an incredible, encyclopedic knowledge about anything in gastroenterology, and he used it to help describe every major complication that could affect the GI tract or the liver.”

Those complications were legion and poorly understood. Take GVHD, a potentially fatal transplant complication that occurs when the donor’s immune cells attack the recipient. Acute GVHD occurs in most transplant recipients, and McDonald routinely saw patients with symptoms of the disease. Patients with the most severe forms of GVHD remain seared in his memory.

But early on it was hard to distinguish between GVHD and other diseases such as, say, widespread infections and damaged blood vessels in the liver, Appelbaum said. McDonald untangled the diagnostic knots.

“Understanding all these different categories was and continues to be incredibly important,” Appelbaum said. “George was such a complete physician and understood so much about basic physiology that he helped us develop better methods to prevent and treat them.”

A student and a teacher

McDonald has always followed his curiosity. In college, he assumed he would go into chemistry. But a summer internship spent trying to synthesize an anti-cancer drug (“I totally failed”) prompted him to apply to med school. He attended Washington University in his hometown of St. Louis. An internship, followed by residency and a fellowship, at the University of Washington brought him to Seattle.

After the fellowship, he established a physiology lab at the VA Hospital. At night he’d consult on transplant patients. All for free.

“This was kind of a hobby. I didn’t submit any bills for my service,” he said. “I was just interested in defining diseases and trying to figure out the pathophysiology of all these complications that we were seeing. That was reward enough.” 

Design of a helical sculpture
In 2005 McDonald submitted this design for a sculpture for the Fred Hutch campus. (It wasn't selected.) "George knows something about everything. He's an engineer, he's a scientist, he's a doctor — he's a Renaissance man," says friend, collaborator and statistician Dr. Ted Gooley.

Treating patients was rewarding as well. Storb and Appelbaum both highlighted his thoughtful, kind approach to their patients. McDonald had a gift for explaining complex science and physiology in ways they could digest.

He taught his colleagues, too. Appelbaum recalls how McDonald always brought a set of colored pens to his consults. “He would draw the exact pathology freehand in his notes, using multiple colors to show you exactly where the ulcer was in the ileum,” he said. “That’s classic George.”

And he taught dozens of fellows and visiting physicians over the years, now specialists scattered around the globe. They all share his relentless curiosity and devotion to basic research, said Dr. David Hockenbery, who was mentored by McDonald.

That could have something to do with his famous shoe test.

“When George evaluates people for fellowships, he always looks at their shoes,” Hockenbery said. “If they swear they’re interested in research and academic medicine but have on a $500 pair of calf-skin Italian shoes, he doesn’t buy it at all. He’s looking for well-worn sneakers.”

McDonald usually wears walking shoes, Hockenbery added. “Nothing Italian, and no loafers.”

Writing the book

McDonald’s last official day at Fred Hutch is Feb. 6. But colleagues will still see him from time to time on campus. He’s still trying to wrap up a few final papers, which will add to the hundreds he’s co-authored with an even larger number of collaborators.

One item is the perfect bookend to a journey that began with the meager insights he found in Index Medicus so many years before. He wrote a chapter on GI and liver complications for all five editions of Thomas’ Hematopoietic Cell Transplantation, the definitive transplant reference named in honor for the same Thomas who made that fateful call.

The chapters sum up everything he's learned in 40 years, patient by patient, trial by trial. And while modest about his role in the transplant “village,” he knows he’s helped make a difference. In 2010, McDonald and several Fred Hutch collaborators compared transplant outcomes between the 1990s and the early 2000s. There was a striking, roughly 50 percent fall in mortality from one decade to another. They’ve since updated this research, finding that over the last decade, mortality after transplant continues to fall and survival improve. 

“And that’s due to a series of little tweaks in how we do things,” he said. “But all those little tweaks sum up to better survival.”

The little tweaks all began, like his career, with an eager leap into the unknown. He’ll take the same approach for his next chapter:

“I like Michelangelo’s dictum ‘ancora imparo — I am still learning.’ I think that’s going to be my motto for retirement.”

Jake Siegel is a former staff writer at Fred Hutchinson Cancer Center. Previously, he covered health topics at UW Medicine and technology at Microsoft. He has an M.A. from the Missouri School of Journalism.

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