It is with deep sorrow that we announce the passing of Dr. Makio Ogawa, a pioneer and a trailblazer in stem cell research, on February 6, 2024, at his home in New Hampshire. He had just celebrated his 84th birthday and was playing Go online. According to reports, his wife Mary-Jane found him peacefully departed when she went to call him for lunch.

Dr. Ogawa, renowned for his contributions to hematopoietic stem cell research, received accolades such as the William Dameshek Prize (1991) from the American Society of Hematology (ASH). While making significant international contributions in the field of hematopoiesis, he also served as a guiding figure to more than 40 Japanese graduate students in the Ogawa Laboratory, helping to bridge the gap between Japan and the United States. He also served as a Regional Editor for the International Journal of Hematology (IJH) (1991–2004), offering insights from a global perspective. Dr. Ogawa’s discussions with Dr. Yataro Yoshida (Kyoto University) could shape the current direction of IJH.

I had the privilege of meeting Dr. Ogawa at a symposium on aplastic anemia held on Mount Hiei, nearly half a century ago. During that time, stem cell research was in its infancy. We were struggling to establish myeloid colonies, let alone erythroid colonies (looking back, issues with CO2 incubators and poor fetal bovine serum were evident). Amidst these challenges, Dr. Ogawa drew attention by successfully forming large erythroid colonies or bursts from cord blood or peripheral blood, suggesting that circulating blood includes hematopoietic stem cells (HSCs) as well as erythroid precursor cells. At around 40 years old, he exuded the aura of a rising star, and many aspired to follow in the footsteps of the young Japanese hematologist making a mark in the United States.

Dr. Ogawa’s journey, as seen in his background (CV Table), started with his graduation from Osaka University Medical School. Despite his deep respect for Professor Yuichi Yamamura, he wanted to learn a more practical, clinically oriented approach rather than an academic one. Thus, he completed clinical training in English at Yokosuka Naval Hospital and subsequently moved to the United States, where he became a clinical fellow at Dartmouth College under the instruction of Dr. Ross McIntyre.

An encounter with a patient who arrived from far away on a snowy day during his early clinical career proved to be fateful. On Christmas Eve, while covering a shift for a female doctor attending a party, he discovered that the patient had IgE myeloma. This led him to contact a well-known immunologist, Dr. Kimishige Ishizaka, who was in Denver at the time. Through his interactions with Dr. Ishizaka, Dr. Ogawa committed to serious research and tried to learn stem cell biology under the mentorship of Professor Ernest McCulloch at the University of Toronto, who proposed the concept of stem cell biology in 1961. Toronto, a mecca for stem cell research then (and now), housed brilliant minds like Norman Iscove and Dr. Connie Eaves in its research institutes. However, Dr. Ogawa recalled that direct involvement in stem cell research was not feasible at the time.

After completing his graduate studies, he received an invitation from the Medical University of South Carolina (MUSC) in Charleston, where he established an independent research laboratory. The research environment at MUSC was not particularly well equipped, with only clean benches and incubators available. Nevertheless, Dr. Ogawa found joy in forging his own path independent from his predecessors in stem cell research.

Analysis of erythroid colonies from 1976 to 1982 was the successful result of collaborative efforts spanning three generations with Dr. Hiroshi Hara, Dr. Kinichi Kidoguchi, and Dr. Takashi Terasawa. Interestingly, this research revealed that erythroblast colonies from adult bone marrow also expressed fetal hemoglobin (HbF), bringing forth the significant theme of hemoglobin switching. This research deepened Dr. Ogawa’s connections with molecular biologists such as Dr. Arthur Nienhuis (NIH) and Dr. George Dover (Johns Hopkins).

In 1980, Dr. Tatsutoshi Nakahata introduced the concept of colonies consisting of multiple cell lineages (GMM colonies) at Ogawa Lab. An amusing incident occurred during this study, when a reviewer questioned whether erythroblasts were present in those colonies. Upon replating, erythroblast colonies indeed appeared, leading to the realization that colonies comprising undifferentiated cells should also exist, and this ultimately contributed to the identification of “blast colonies.” The reviewer’s skepticism actually ended up propelling the progress of the research.

The theme assigned to us (Toshio and Junko Suda) involved tracking the differentiation of paired daughter cells using blast colonies. This research, detailed in Dr. Ogawa’s NIH grant application, progressed exactly as outlined in the proposal. When I raised some questions, he responded with, “I had already considered that,” showcasing his sharp foresight, akin to a skilled move in Go or Shogi. From this experiment, Dr. Ogawa proposed a stochastic model of differentiation, opposing the prevailing model that cytokines like erythropoietin induce differentiation. According to his model, these cytokines merely act as proliferative signals, and cellular differentiation occurs autonomously and randomly. This study demonstrated the possibility of manipulating hematopoietic stem and progenitor cells at the single-cell level and revealed the possibility of asymmetric cell division, though the mechanism remains unclear.

Dr. Ogawa preferred submitting papers to the Journal of Cellular Physiology, where Professor McCulloch served as the editor-in-chief.

(we didn’t care much about Impact Factor back then). Professor McCulloch made an unforgettable comment: “The results match the Stochastic Model of differentiation, but it cannot be claimed to be proven.”

Many postdocs, including myself, received a lot of advice from Dr. Ogawa, such as “The choice of what to do and what not to do is important,” “Focus is crucial,” “Even if it’s minor at first, conduct original research,” and “To achieve that, read the data carefully and repeatedly.” There were even stories of his mentor, Professor McCulloch being so deep in thought that he found himself accidentally chewing on the chalk he was holding.

In the early 1980s when I studied abroad, there were visits from Professor McCulloch, David Golde (UCLA Professor), Curt Civin (Johns Hopkins Professor), as well as Yūichi Yamamura (Osaka University President), Tadamitsu Kishimoto (Osaka University Professor and a classmate from Dr. Ogawa’s Osaka University days), Fumimaro Takaku (University of Tokyo Professor), and Teruko Ishizaka (Colorado University immunologist). This gave me a sense of Dr. Ogawa’s strong network.

Charleston, where these events took place, is a picturesque tourist city on the coast, known as the birthplace of the Civil War. Later on, Dr. Ogawa continued hematopoietic research until the age of 70. One memorable aspect of his brilliant research career is that after retirement, he left Charleston and moved to a town near Hanover, New Hampshire, filled with memories with his wife. Living in a beautiful house surrounded by woods, he spent his time in a “quiet life.” Two years ago, I was fortunate to have the opportunity to have a leisurely conversation with Dr. Ogawa, who was leading a tranquil life in nature-rich New England.

Kendo, Professor Ogawa’s chosen hobby, evidently served as a guiding principle in his lifestyle. Standing resolute with a composed demeanor, attentively observing the movements of his metaphorical opponents (nature), and decisively striking when the moment was opportune—he appeared to have realized such a fulfilling existence.

I sincerely offer my heartfelt prayers for Professor Ogawa’s peaceful rest.

July 1968: Fellow in Internal Medicine, Dartmouth College, USA.

October 1973: PhD, Faculty of Medicine, University of Toronto, Canada.

July 1973: Associate Professor of Internal Medicine, Medical University of South Carolina, USA.

July 1977: Assistant Professor of Internal Medicine, Medical University of South Carolina, USA.

July 1980: Professor of Internal Medicine, Medical University of South Carolina, USA.

1991–2004: Regional Editor for the International Journal of Hematology.

1989: Veteran Affairs William S. Middleton Award.

1991: William Dameshek Award, American Society of Hematology.

1992: Governor’s Award, South Carolina, USA.

1994: Kitasato–Behring Award.

2001: Metcalf Lecture Award, International Society for Experimental Hematology.

American Society of Hematology.

American Society for Clinical Investigation.

Association of American Physicians.

International Society of Experimental Hematology (President, 1989).