Encyclopedia of Pathology

Living Edition
| Editors: J.H.J.M. van Krieken

Nakane, Paul Kazuo (1935-Present)

  • Fred T. BosmanEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-28845-1_4033-1


Alkaline Phosphatase Conjugate Freeze Tissue Section Lectureship Award Bifunctional Reagent Immunopathological Study 
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English Names

Paul Nakane

Original Names

Paul Kazuo Nakane

Date, Country, City of Birth

1935, Yokohama, Japan

Current Domicile

Cambria, CA, USA

History of Life

Paul K. Nakane is born in Yokohama, Japan, in 1935 to Dr. and Mrs. T. Nakane. He graduated from Huntingdon College, Montgomery, Alabama, in 1958 and received his Ph.D. from Brown University in 1963. He held faculty positions at Stanford University, the University of Michigan, and the University of Colorado Health Sciences Center, the latter as professor of Pathology in the department chaired by G. Barry Pierce.

He returned to Japan in 1982 as Director of the Medical Research Institute and Chair and Professor of Cell Biology at Tokai University School of Medicine. In 1989 he assumed a position as Chair and Professor of Anatomy at Nagasaki University School of Medicine.

Paul Nakane returned to the USA in 1997 to serve as a Director of Diagnostics at a pharmaceutical company, and in 2003 he joined California Polytechnic State University at San Luis Obispo, California, as research professor. His studies focused on the development of methods for in vivo histochemistry.

Paul Nakane has been a highly respected member of the international community of scientists interested in developing methods to visualize molecular process at tissue level. For his pioneering work in immune (electron) microscopy, he received the David Glick Lectureship Award (1988) and the homonymous Paul K. Nakane Prize (2004) from the International Federation of Societies for Histochemistry and Cytochemistry. He was a recipient of a Royal Microscopic Society Lectureship in 2000 and of the George Gomori Award in 2007 from the Histochemical Society, who in 2008, in recognition of his many contributions to science, awarded him honorary lifetime membership.

Paul and Cynthia Nakane continue to enjoy life in the coastal town of Cambria in California.

Main Achievements to Medicine/Pathology

It is hard to imagine what pathology would look like in the twenty-first century if immunohistochemistry had not been developed. The idea to couple antibodies with a label to visualize where they bound in frozen tissue sections had been pioneered by Alfred Coons in the early 1940s, using fluorescein as fluorochrome. Working with early fluorescence microscopes, however, was cumbersome, and this methodology was further developed for use in immunological tests, but it did not gain ground in histopathological diagnosis. This changed significantly with the development of dichroic mirrors by the Dutch microscopist Bas Ploem in the early 1960s, which revolutionized fluorescence microscopy. The Leica company produced the first fluorescence microscopes equipped with this technology under the eponymous label of “Ploemopak.” This facilitated fluorescence microscopy, and gradually immunofluorescence became an appreciated tool in immunopathological studies. For diagnostic problems in histopathology, however, the autofluorescence introduced in tissue by formalin fixation and the need for a fluorescence microscope represented major hurdles.

And then in 1966, Paul Nakane and Barry Pierce introduced the, now classic, enzyme-labelled antibody method. It is not inconceivable that Barry Pierce had the idea (although he never claimed this), but most certainly it was Paul Nakane who invented a method to conjugate an enzyme to an antibody while maintaining both antibody reactivity and enzyme activity. Initially alkaline phosphate was tested along with horseradish peroxidase (HRP), both enzymes readily available on the market. To couple antibodies with the enzyme, bifunctional reagents were used, either p,p′-difiluoro-m,m′-dinitrodiphenyl sulfone or 1-ethyl-3-(3-dimethylamino propyl) carbodiimide. The alkaline phosphatase conjugates appeared to have very limited stability and so in the end preference was given to HRP. The use of enzymes as tracers for antibodies and antigens, and the methods to label them, has led to the developments of methods such as ELISA, Western blot, Southwestern blot, Southwestern histochemistry, and chromogenic in situ hybridization. It was not only Nakane’s invention that advanced the field. Stratis Avrameas introduced glutaraldehyde conjugation in 1997 and Ludwig Sternberger the unlabeled peroxidase-anti-peroxidase immune complex method in 1970. This methodology revolutionized pathology dramatically, and presently no self-respecting pathology service would be without well-equipped immunohistochemical facilities. Even Paul Nakane could not have dreamt of the impact his invention would have on the practice of pathology.


References and Further Reading

  1. Avrameas, S., & Lespinats, G. (1967). Enzymes coupled to proteins: Their utilization for the detection of antigens and antibodies. Comptes Rendus de l’Académie des Sciences Hebdomadaires Seances de l’Académie des Sciences, 265, 1149–1152.Google Scholar
  2. DeLellis, R. A., Sternberger, L. A., Mann, R. B., Banks, P. M., & Nakane, P. K. (1979). Immunoperoxidase technics in diagnostic pathology. Report of a workshop sponsored by the National Cancer Institute. American Journal of Clinical Pathology, 71, 483–488.CrossRefPubMedGoogle Scholar
  3. Kawarai, Y., & Nakane, P. K. (1970). Localization of tissue antigens on the ultrathin sections with peroxidase-labeled antibody method. Journal of Histochemistry and Cytochemistry, 18, 161–166.CrossRefPubMedGoogle Scholar
  4. Nakane, P. K., & Pierce Jr., G. B. (1966). Enzyme-labeled antibodies: Preparation and application for the localization of antigens. Journal of Histochemistry and Cytochemistry, 14, 929–931.CrossRefPubMedGoogle Scholar
  5. Nakane, P. K., & Pierce Jr., G. B. (1967). Enzyme-labeled antibodies for the light and electron microscopic localization of tissue antigens. Journal of Cell Biology, 33, 307–318.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Nakane, P. K. (1968). Simultaneous localization of multiple tissue antigens using the peroxidase-labeled antibody method: A study on pituitary glands of the rat. Journal of Histochemistry and Cytochemistry, 16, 557–560.CrossRefPubMedGoogle Scholar
  7. Nakane, P. K. (1971). Application of peroxidase-labelled antibodies to the intracellular localization of hormones. Acta Endocrinologica. Supplementum, 153, 190–204.PubMedGoogle Scholar
  8. Nakane, P. K., & Kawaoi, A. (1974). Peroxidase-labeled antibody. A new method of conjugation. Journal of Histochemistry and Cytochemistry, 22, 1084–1091.CrossRefPubMedGoogle Scholar
  9. Nakane, P. K. (1975). Recent progress in the peroxidase-labeled antibody method. Annals of the New York Academy of Sciences, 254, 203–211.CrossRefPubMedGoogle Scholar
  10. Sternberger, L. A., Hardy Jr., P. H., Cuculis, J. J., & Meyer, H. G. (1970). The unlabeled antibody enzyme method of immunohistochemistry: Preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. Journal of Histochemistry and Cytochemistry, 18, 315–333.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  1. 1.Department of PathologyUniversity Medical Center LausanneLausanneSwitzerland