Restless Giant
They lived their lives as if their sights were set on the clouds beyond the hill they were climbing.
Akira Kurosawa, Something Like an Autobiography
If Bart Barlogie were a fictional character, it would be hard to figure out if he was hero or villain. With him, there was no middle ground. An intellectual pioneer like Robert Kyle, he couldn’t have been more different.
Barlogie instilled an almost mystical faith among his patients and their families at the University of Arkansas for Medical Sciences in Little Rock. Out of public sight, he returned their devotion with a confidence that made them feel they were at the center of his universe, his grasp of the science and treatment, and the commitment it demanded of everyone.
That didn’t stop some colleagues from demonizing him behind his back, claiming his patients were guinea pigs in risky experiments. They couldn’t argue the same publicly. Despite the suffering many of his patients seemed to go through under his care, a concept he called total therapy: hit the disease hard in the beginning with everything you know that works most effectively, they accepted the risks knowing more and more of them seemed to be doing better than average.
In more and more cases, much better. But the only way to fully appreciate why, a short consideration of Barlogie’s life before Arkansas is essential.
Windswept, isolated plains in North Dakota like those nurturing a young Robert Kyle would likely have been unimaginable to a young Bartholomeus Barlogie growing up in the post-World War II rubble of Krefeld, Germany, a city with skilled workers on the west bank of the Rhein River.
Located to the west of the Ruhr Valley, Germany’s industrial heart, and just north of two of its most economically powerful cities, Düsseldorf and Cologne, Krefeld practically invited Allied bombing and was obliged with near total destruction.
Barlogie’s father died in the war. When his mother remarried, his stepfather gave him stability and a last name. Looking back at his early life before moving to the U.S. in 1974, Barlogie was an embodiment of confidence of the post-war German economic miracle. Science and medicine became his refuge from the turmoil of Cold War politics that seemingly invaded everyone’s lives around him. School seemed almost too easy for him as he studied at some of the most prestigious universities in Germany before ending his studies as a medical resident in Münster.
A visiting lecture by Freireich in Münster inspired Barlogie. On his way to becoming “the father of modern leukemia,” Freireich championed using high doses of chemotherapy, which many contemporaries considered barbaric. Regardless, this approach would play a pivotal role in raising childhood leukemia survival rates from single digits to more than 90%, a fact he recalled as “magical” for the rest of his life.
Following the lecture, Barlogie asked Freireich about coming to work in Houston. They clicked, stayed in touch, and relatively soon, Barlogie was on a plane for Houston. Freireich had a knack for attracting and recruiting the best minds; MD Anderson provided the resources and a platform to attract them. Experts – mostly, but not exclusively male, as was common then – came not just from the United States, but from Australia, India, Argentina, Germany, and the Netherlands when Barlogie arrived. Today, walking through the corridors of MD Anderson, one can’t help but see it as something of a medical United Nations…with a slight Texas drawl.
Barlogie was not coming just to learn, though. He brought with him knowledge and passion for something that was quite new at the time, not just at MD Anderson, but around the globe: flow cytometry, a method to see “deep” into cells to identify and measure its components.
Flow cytometry’s historical roots include Paul Ehrlich’s linking of specific affinities of industrial dyes to cells. And Robert Kyle’s application of electrophoresis to identify and determine the number of their various components, which led to his discovery of the M-spike in serum, the classic marker of myeloma.
MD Anderson had no capabilities to perform flow cytometry. So Barlogie brought his own with him from Germany. Sundar Jagannath, who joined the MD Anderson faculty in the late 1970s and is now the influential head of New York’s Mount Sinai Hospitals myeloma program at its Tisch Cancer Institute, recalled, “he had his own flow cytometry, whether he paid for it, I don’t know.”
After arriving, Barlogie was assigned to do clinical work in Houston’s Memorial Hermann Hospital, focusing on hypothermia, while he was doing research at MD Anderson. Shortly thereafter, Barlogie was assigned to do both research and clinical care at MD Anderson.
In myeloma.
Considered by many as something of a professional dead end, myeloma had not been in Barlogie’s career plans. He was wanted to join Freireich and be integral in curing adult and childhood leukemias. Whether or not Freireich saw something in Barlogie to give him myeloma as a puzzle to solve, looking back, the choice had an almost poetic quality.
Barlogie applied Freireich’s mindset for aggressive treatment philosophy for leukemias to myeloma, the antithesis of Kyle’s “watch and wait.” His impatient, driving compulsion was closer to “seek and destroy.” He saw what was being achieved in childhood leukemias every day at MD Anderson. Why couldn’t it be done in myeloma as well?
He would work closely with Raymond Alexanian, whose idea of the combination melphalan-prednisone had by then become a standard treatment for myeloma. Although they had opposite temperaments, what differences in treatment approaches they had, never got in the way of individual patient care.
Barlogie became intrigued with a new treatment after attending a medical conference in England in the mid-1980s. Although it was cutting edge, the theory behind it could be traced to Hippocrates, Paul Ehrlich, James Till and Ernest McCullough, and Don Thomas’s “living medicine”: autologous stem cell transplantation (ASCT). As Jagannath remembered it, “He immediately came back and wanted to do auto transplant for myeloma.”
One of the speakers was Raymond Powles from the Royal Marsden Hospital in London, the world’s first hospital dedicated to treating cancer (and where Brian Novis and his fiancé Susie met Brian Durie) was one of the speakers. While Don Thomas had been establishing bone marrow transplantation (BMT) for years in the United States, Powles conducted the first successful autologous stem cell transplant (ASCT) in Europe in 1974. Applying the word “successful” to BMT and especially myeloma, is very relative and full of potential catastrophes such as graft-versus-host-disease (GvHD).
BMT had been showing more success in blood cancers – not myeloma – and was becoming more prevalent. Although Till and McCullough had proven the existence and function of stem cells, it was still mostly theory; not much had moved to clinical practice in real patients. As Jagannath recalled the era when he joined MD Anderson’s faculty, “we did not know stem cells at that time, there was no antibody, it was a bone marrow transplant.”
Powles collaborated with Tim McElwain, another London-based myeloma expert, to perform the first autologous hematopoietic stem cell transplant in 1983. They extracted bone marrow and administered high doses of intravenous melphalan slowly over four days to wipe as much of a patient’s immune system as possible. The bone marrow was put into a centrifuge to separate stem cells from the rest of the marrow and then reintroduced in the same patient after the high dose therapy of melphalan. The goal was to have these stem cells repopulate the depleted marrow to eliminate myeloma cells.
The entire procedure took three weeks or more, all of it as a hospital in-patient. Recovery could be up to six months. And relapse was inevitable. The best that could be hoped for was that ASCT would delay the disease indefinitely.
Upon his return to Houston, Barlogie realized the problem to myeloma treatment was it almost always had side effects, some treatable, some not, most being complicated with an ever-present prospect of death. Chemotherapy, for example, often seemed worse than the disease it was supposed to fight. Side effects including hair loss, nausea, peripheral neuropathy making it harder to walk and touch, and constipation or diarrhea. Not to mention how people often responded, ranging from dread to pity.
Plus, the combination had one great drawback: myelosuppression. At the same time the drug combination was attacking myeloma cells, it also caused collateral damage to the bone marrow, inhibiting its ability to create the components of blood. Administering it to patients was the classic conundrum of chemotherapy’s history: trying to kill more of bad cells while, at the same time, not kill too many good ones. Barlogie looked for alternatives, new combinations.
He knew about vincristine. It came from, like so many cancer drugs, an odd, counterintuitive source. As Siddhartha Mukherjee explains in The Emperor of All Maladies, it as “a small, weedlike creeper with violet flowers and an entwined, coiled stem” which “had been discovered in 1958 at the Eli Lilly company through a drug discovery program that involved grinding up thousands of pounds of plant material and testing the various extracts.” Vincristine “at small doses was found to kill leukemia cells.” It was not myelosuppressive, but also not effective on its own.
He also knew about another chemotherapy, doxorubicin, better known by its commercial name, Adriamycin. Used for a variety of cancers, its major side effect was potential heart damage. Trading a heart condition for cancer didn’t inspire patient confidence, but experience showed slow, intravenous administration was dramatically better than direct, shot-like infusion.
Finally, he needed a steroid, which acts like a turbo-booster to accelerate and intensify therapeutic effects of steroids. Dexamethasone is six times as potent as prednisone. VAD was born. The combination used the commercial name Adriamycin to distinguish it from dexamethasone and became known as VAD.
It met two of Barlogie’s goals: avoid myelosuppression and make the combination as potent as possible. The regimen was successful in “knocking myeloma numbers down,” shorthand for stopping and reversing some of myeloma’s aggressiveness but, like melphalan, only for limited time.
Alexanian still was very much in the “watch and wait” camp of myeloma treatment. Even though he didn’t completely buy into Barlogie’s “search and destroy” approach, they had a successful partnership, making MD Anderson a destination with the full range of treatments available at the time – admittedly not many – for myeloma patients throughout the nation.
By 1989, institutional politics making life difficult for Freireich caused many of his staff to disperse to other institutions, mostly in the United States. One went to the University of Arkansas for Medical Sciences and recruited Barlogie to become chief, Barlogie recruited Jagannath to run its clinical program, and Jagannath recruited Sharon Tindall, to establish the research program.
Over the next two-plus decades, Barlogie and his team would transform the myeloma landscape. We’ll revisit this over the coming months many times.
One myth that exists about Barlogie and Arkansas is only partly true: that Sam Walton, founder of WalMart, had myeloma, Barlogie was his physician, and he donated a great deal to the University. In essence, Walton brought Barlogie to Arkansas.
The truth is Walton first had leukemia and was treated at MD Anderson. He was later diagnosed with a second malignancy, myeloma, and was referred to Little Rock. Barlogie was already in Arkansas when Walton came to be treated there.
Lastly, having little to do with the substance of this story, but still important in its own way, Barlogie’s last name is NOT pronounced as Bar-LOW-ghee. To enunciate it correctly, visualize descending steps in your mind when saying it out loud, BAR-luh-ghee. It’s a minor thing, but as one who has had his last name butchered for a lifetime, it IS something.
The most important fact to remember is this: No single individual did more than Bart Barlogie to give the myeloma research and treatment status quo a proverbial kick in the pants. No one.
I liked the story.
As someone who is the husband of one of Bart's former patients, I can say that you described him well.