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Summon up the Blood: in Dogged Pursuit of the Blood Cell Regulators

Professor of Medicine, Emeritus, University of Washington Member, Fred Hutchinson Cancer Research Center Nobel Laureate, Medicine/Physiology, 1990

In Summon up the Blood, Don Metcalf gives a personal account of the long and tedious path leading to our present knowledge of growth factors and cytokines. It began with a visit to his laboratory by Ray Bradley who brought a set of Petri dishes containing semisolid agar cultures of mouse bone marrow with surprising small colonies. The colonies were made up of clusters of hematopoietic cells. This event was another example in science of "a picture is worth a thousand words." As one who took Puck's course in Colorado and attempted liquid marrow cultures in the 1950s, I can understand why it changed Don's life, and initiated studies that were to bring him fame for the betterment of all of us. Don describes with sadness the friction that arose with the Israeli Group of Sachs et al., who apparently made simultaneous observations of marrow colonies.

Don then describes the observation of colony stimulating factor (CSF) and the confusion about what it was and how it acted. A big step forward came from identification and purification of a CSF from human urine. Further confusion followed with recognition that there were several CSFs. The terminology of the various factors eventually became known as M-CSF, GM-CSF, and G-CSF. The book gives the experience of the Melbourne team as they worked out the confusions and contradictions.

A unique aspect of the studies in Melbourne was that Dr. Metcalf did the microscopic scoring of the colonies himself. This allowed him to keep a watchful eye on the quality of the cultures. It allowed him to recognize novel colonies or phenomena and on many occasions to recognize novel hematopoietic regulators. That the leader of the team would do this himself over the years probably explains why Don never rose to the level of his incompetence as has happened to others in hematology who go on to become chairmen or deans.

Enter molecular biology. The cloning and manufacture of the CSFs through recombinant technology made them available in quantity. For the first time a number of informative studies could be done and the stage was set for studies in human beings. The clinical importance of the factors was quickly recognized. Therein lies a sad part of the story in the Metcalf book. The Melbourne team did not win the race to the patent office. At that time, most academic scientists were not oriented toward commercial development of their scientific discoveries. Now it is widely recognized that the patent application takes precedence over publication in scientific journals. Don Metcalf had to watch others gain economic harvest from the seed of his research. We all know that scientific progress is the result of work by many investigators coming together. The patent office is all or none; you either have the patent or you don't. Commercialization brings money and practical progress at the expense of collegiality and cooperation.

Don describes the cloning and characterization of the receptors for the CSFs and the numerous informative studies of gene deletion in mice. Sometimes the details of the studies described throughout the book are too much for the casual reader and are perhaps best suited to those who work in the field. Even so, one cannot escape the fact that Don Metcalf was, and is, a dedicated worker and deep thinker. He did things himself. The style is sometimes abrasive, but always informative. Finally, it is clear that Don Metcalf is not through. He continues to work in the laboratory with his own hands. We can look forward to continued production and innovation from Don and his group.

FOOTNOTES

By Donald Metcalf. 214 pp., illustrated. Miamisburg, Ohio, AlphaMed Press, 2000. (Hard Bound) $49.95, ISBN: 1-88085-427-9; (Soft Bound) $29.95, ISBN: 1-88085-428-7

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