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Peter C. Nowell, MD (1928-2016): Loss of an icon and iconoclast
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I usually am saddened when I read of the passing of a scientific icon.
However, the loss of Peter C. Nowell, MD, on Dec. 26 at the age of 88 years represented so much more, and it was so well cast in the gracious and heartfelt obituary from Mark I. Greene, MD, PhD, FRCP, and Jonni S. Moore, PhD, that appeared in the March issue of Science.
Nowell represented a figure that may well cease to exist in the biomedical society of the future: a brilliant scientist who created outstanding research in so many domains, while serving as an extraordinary mentor, teacher, true gentleman, family man and friend, as eloquently described by Greene and Moore.
To prepare this editorial, I carried out a PubMed search on “Nowell PC” and discovered 313 papers published between 1956 and 2011, the last representing a symposium commemorating the 50th anniversary of the discovery of the Philadelphia chromosome.
I also did some due diligence and learned that Nowell received his medical degree from University of Pennsylvania in 1952 and completed a residency in pathology at Presbyterian Hospital, followed by 2 years at the United States Naval Radiological Defense Laboratory in San Francisco. He then moved back to University of Pennsylvania, and spent the remainder of his career there.
Nowell’s amazing career showed the interplay between immense precision in molecular diagnostics — a field that he helped to evolve — apposed with extraordinary out-of-the-box scientific conceptualization and execution.
The first of his papers that I could find focused on the use of X-irradiated mice to study long-term survival of injected bone marrow progenitor cells. He used that model further to study the distribution and outcome of injected bone marrow cells and the pattern of tumor incidence in long-term follow-up.
Nowell’s group also demonstrated the suppression of wound healing by graft-versus-host reaction in animals transplanted with marrow progenitors. This work served as a harbinger of the whole domain of clinical bone marrow transplantation.
His interest in radiobiology led to studies of the biological impact and applications of X-rays and fast neutrons, and it also elucidated the process of radiation carcinogenesis.
However, his major focus changed again following his collaboration with David A. Hungerford, PhD, to perform some of his most important work, the identification of the Philadelphia chromosome, the exact nature of which was later defined by the late Janet D. Rowley, MD.
Nowell’s work then centered on tumor heterogeneity and associated genetic changes, and he evolved the iconoclastic concept of clonal evolution of tumor cell populations.
In a highly productive sequence, Nowell and his colleagues demonstrated the coexistence of myeloid and lymphoid neoplastic subpopulations in chronic myelogenous leukemia, identified cytogenetic changes and oncogenes in Burkitt lymphoma and melanoma, and advanced the molecular bases for T- and B-cell lymphomas. They also showed the production of granulocyte colony–stimulating factors by solid tumors, studied mechanisms of tumor progression, and demonstrated that the phosphorylation process induced by epidermal growth factor alters oncogenic and cellular function of the NEU oncogene.
If that was not enough, they went on to study autoantibodies to red cell antigens, the genomic features of preleukemia and myelodysplastic syndrome, and demonstrated the paracrine and autocrine regulation of T-lymphocyte proliferation by TGF-beta.
Nowell’s last report of original work showed the transfer of trisomy 8 from a donor to a bone marrow transplant recipient, emphasizing the importance of full pretransplant characterization of the bone marrow donor to avoid misinterpretation of isolated posttransplant gene abnormalities as necessarily being unstable harbingers of future trouble.
Photo credit: Penn Medicine.
Despite the risk of appearing dreadfully lame, I wish to chronicle just some of the extraordinary list of his published papers — namely, 41 in Proceedings of the National Academy of Sciences, 20 in Cancer Research, 17 in Blood, 17 in The Journal of Immunology, 13 in Science, 13 in Journal of the National Cancer Institute, six in The Journal of Experimental Medicine, three in The Journal of Clinical Investigation and three in Nature, to list just a few. Although not consistent with editorial policy in HemOnc Today, we have left the titles of the listed references below in place to emphasize the range, importance and creativity of Nowell’s work.
In an era that focuses on cost, stringent and narrow thinking, the need for extensive preliminary data prior to scientific funding, and which certainly is fostering burnout in the individuals formerly termed triple-threats, it is hard to imagine the emergence in biomedical research of individuals of the caliber of Peter Nowell.
I did not have the privilege of knowing him personally, but I wish I had.
Rest in peace, Dr. Nowell, and thanks for sharing the products of a grand and science-altering career.
References:
Cole LJ and Nowell PC. Radiation carcinogenesis: The sequence of events. Science. 1965;150:1782-1786.
Frey NV, et al. Trisomy 8 in an allogeneic stem cell transplant recipient representative of a donor-derived constitutional abnormality. Am J Hematol. 2008;doi:10.1002/ajh.21268.
Greene MI and Moore JS. Science. 2017;doi:10.11/26/science.aam9738.
Nowell PC. The clonal evolution of tumor cell populations. Science. 1976;194:23-28.
Nowell PC and Hungerford DA. Chromosome studies on normal and leukemic human leukocytes. J Natl Cancer Inst. 1960;25:85-109.
Nowell PC, et al. Growth and continued function of rat marrow cells in x-radiated mice. Cancer Res. 1956;16:258-261.
For more information:
Derek Raghavan, MD, PhD, FACP, FRACP, FASCO, is HemOnc Today’s Chief Medical Editor for Oncology. He also is president of Levine Cancer Institute at Carolinas HealthCare System. He can be reached at derek.raghavan@carolinashealthcare.org.
Disclosure: Raghavan reports no relevant financial disclosures.