Leonard Herzenberg, PhD

2002 Edwin F. Ullman Award

The the Association for Diagnostics & Laboratory Medicine (formerly AACC) Awards Committee is pleased to announce that Leonard A. Herzenberg, PhD, is the recipient of the 2002 Edwin F. Ullman Award, sponsored by Dade Behring, Inc. Dr. Herzenberg will be honored at the upcoming Oak Ridge Conference in April. The Awards Committee selected Dr. Herzenberg for this award because of his development of monoclonal antibodies and the Fluorescence Activated Cell Sorter (FACS) as complementary tools for biomedical studies. Dr. Herzenberg is Professor of Genetics, Emeritus, at Stanford University, Stanford, CA.

In the early 1960s, Dr. Herzenberg recognized that studies of normal and neoplastic cells would be severely limited until technology capable of recognizing and sorting different kinds of mammalian cells was developed. At the time, fluorescent-labeled antibody preparations were being used to distinguish various blood and other cells from one another under the fluorescence microscope. However, there was no way of isolating these cells from one another so that their individual functions could be studied. Responding to this need, he drew together an engineering team to build an instrument capable of sorting viable cells with a desired level of associated fluorescence into a test tube for further analysis.

The importance of Dr. Herzenberg’s vision in developing this FACS as a central tool for characterizing normal and neoplastic cells was recognized by the National Cancer Institute (NCI), whose support over a period of 15 years helped him develop the basic methodology for FACS use and to improve the instrumentation to make it more versatile for biomedical studies. By the late 1970s, FACS instruments had been built and sold to laboratories all over the world. However, Dr. Herzenberg was keenly aware that the utility of these instruments was constrained by the lack of consistent reagents for detecting cell surface markers that could distinguish different types of cells. Thus, when he heard that Dr. Cesar Milstein had succeeded in generating immortal cell lines that could produce large amounts of monoclonal antibodies, Herzenberg immediately arranged a sabbatical leave so that he could learn this technology from Milstein.

Returning from Milstein’s laboratory in 1987, Herzenberg led his colleagues in the development of fluorescent-labeled monoclonal antibody reagents, which replaced the conventional antibody preparations that had been used previously, with great difficulty, to identify and sort functional subsets of mouse lymphocytes. With the new monoclonal reagents, Herzenberg and his group rapidly extended the functional characterization of the mouse lymphocyte subsets and, when supplied by colleagues at the Sloan Kettering Institute with monoclonal antibodies to human lymphocyte surface antigens, identified the human homologs of the functional murine subsets. These studies, which laid the foundation for modern approaches to understanding the immune system, also provided the first clear demonstration of how monoclonal antibodies and the FACS can be used as complementary tools for biomedical and immunologic biomedical studies.

In another lasting contribution, Herzenberg recognized that neither the FACS nor monoclonal antibodies would be useful for basic research or clinical applications unless both the instruments and the reagents were produced commercially by companies capable of scaling up to meet demand. Thus, he stimulated and oversaw the development of a competitive flow cytometry industry, including commercial sources capable of delivering high-quality monoclonal reagents labeled with fluorochromes for FACS use. His contributions in this area, begun in 1970, define Herzenberg as one of the early pioneers in the modern biotechnology industry and, most importantly, as a practical visionary whose work has made years of fruitful research possible in laboratories throughout the world.

Finally, foreseeing the role that FACS would one day play in medicine, Herzenberg explicitly laid the groundwork to make FACS technology broadly usable at the clinical level. Today, the fruits of these efforts are visible in a wide variety of clinical applications, including CD4 T-cell monitoring in HIV infection, classification of leukemias and other tumors, tumor staging by cell cycle analysis or surface marker expression, isolation of stem cells for transplantation, and monitoring of the progression of bone marrow transplants. In addition, the current use of monoclonal antibodies to treat diseases such as B-cell lymphoma and rheumatoid arthritis owes much to both Herzenberg’s FACS technology and his development, in collaboration with Drs. Vernon Oi and Sherry Morrison, of molecular methods for producing the "humanized" chimeric antibodies that are central to these highly successful therapies. Although Herzenberg did not directly participate in most of the clinical studies that utilized these methodologies, it is safe to say that they would not exist today if it were not for Herzenberg’s lifelong attention and contributions to the development and deployment of FACS and monoclonal antibodies in the service of science and medicine.