On January 20, 2011 Ernest (“Bun”) McCulloch passed away. Although Bun was known to the young generation of stem cell researchers only by reputation, for those of us who knew him “back then” he was an icon. “Back then” was the 60s and 70s when the group led by Bun McCulloch and Jim Till conducted experiments that led to the concept of stem cells as the source of all cell types in the blood-forming system, proved their existence, described their properties and set the stage for the life-saving procedure of bone marrow transplantation.
Back then we didn’t think much about stem cells in other tissues, and it was more than 15 years before stem cells were identified and characterised in other tissues and in the developing embryo.
Back then I was a PhD student under the supervision of Jim Till. I had come from a physics background as had Jim. Dr. McCulloch, as I called him back then, was a haematologist, a visionary, a descriptive scientist who loved to dream about the art of the possible. His knowledge of the blood-forming system was prodigious, but he was not content with its description. He wanted to know how it developed and how it sustained itself. Jim Till, being a quantitative scientist was the driving force behind the idea that to understand the biology required quantitative measurements.
So when nodules of growing cells were seen in the spleens of irradiated mice who had received bone marrow transplants, it was the two of them together who realized that these could be clones of cells derived from multi-potential precursors. We didn’t use the term “stem cells” back then. Together they set out to develop the spleen colony assay as a quantitative assay for stem cell number, to demonstrate the presence of multiple cell types in the colonies through detailed cytology and to prove that the colonies were derived from single cells. It was a very productive time, with many graduate students and post-doctoral fellows contributing to the effort. You will recognize some of the names – Andy Becker, Allen and Gillian Wu, Ron Worton, Paul Austin, Don Sutherland, Norman Iscove, Allan Bernstein, Bob Phillips, Rick Miller, and somewhat later Connie and Allen Eaves. Many of them went on to train the next generation of stem cell biologists.
At the beginning I was afraid of Dr. McCulloch, so I stuck to getting advice from Dr. Till. The odd time I did speak to him, I felt that he was thinking so far ahead of me that I struggled to understand. Slowly, after a great many weekly group seminars (held in the office of Lou Siminovitch until we outgrew it) I began to be comfortable speaking briefly to Dr. McCulloch, but still didn’t venture into the inner sanctum of his office. Finally, one day after I had generated my first substantial results I presented them to Jim who suggested that I tell Bun as well. I made an appointment and went to see him. He listened, agreed on the importance of the work and without hesitation began to suggest future experiments – dozens of them – so many I couldn’t keep track. This was my first real encounter with the brilliant mind and quick intellect of Bun McCulloch.
Soon I was making regular visits to his office.The next memorable encounter was when I wrote my first paper on stem cells. Like all graduate students, my first paper was way too long and had unnecessary detail that only I deemed to be important. Jim had told me that, and suggested ways to improve it. Bun had received a copy of the manuscript and invited me to his office. He agreed with Jim about the unnecessary detail, and asked if I would like to know how he would write it. I said yes. So, he picked up his Dictaphone and in the next 20 minutes he paced the floor in his office while he dictated a manuscript from start to finish. In those 20 minutes he transformed my pedantic, thoughtful, careful, and fully detailed manuscript into a lively, punchy and dramatic account demonstrating that stem cells defined by the spleen colony assay are distinct entities from the other known precursor cells of the blood-forming system. I was transfixed. It had never occurred to me that anyone could do that. To be sure, his dictated version needed some editing and polishing, but the essence of what he dictated remained intact. It was a valuable lesson, and it completely changed my concept of how to write a scientific paper, even though I never did learn to dictate them in 20 minutes.
Even though Bun had been retired for many years, he will be missed by all of us who knew him well and admired his intellect, his dedication and his profound influence on the field of stem cell biology. For Jim Till, I am sure it will be like losing a twin who for many years had been joined at the hip. And for the younger generation of stem cell scientists it will be a time to pause and reflect on those early experiments, carried out long before the term “stem cell” was a household word, and long before the profound importance of stem cells was recognized. Bun and Jim were true pioneers whose work dictated how we think about the human body, its development and its replenishment. Bun can rest knowing that he truly made a difference.
-- Ron Worton, former Scientific Director of the Stem Cell Network
I invite additional memories, thoughts and comments to this blog as a public, scientific memorial of the incredible Bun McCulloch.