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Tired Eyes: The Nuclear Era and Some Good Ole Ingenuity, The Story of FACS
Fluorescently activated cell sorting (FACS) is used around the world to subdivide heterogeneous populations of live cells often derived from blood. This flexible application, often utilized by immunologists, would not have been possible if it had not been for Leonard Herzenberg's willingness to be a life-long student.

Leonard was born November 5, 1931 in Flatbush Brooklyn, where he attended Brooklyn College and majored in Biology. He later earned his PhD at Cal Tech in Biochemistry and Immunology. Herzenberg then completed his American Cancer Society postdoc in Paris. He then joined Stanford's newly opened medical school in the department of genetics.

Leonard Herzenberg, Stanford University School of Medicine.
During a long session of counting fluorescently-labeled cells, Leonard longed for an instrument that could expedite this highly mundane task. It turned out he was asking that question at the perfect time, as several other scientists were beginning to develop machines that could sort cells and particulates by volume. The need for this type of device had grown out of the atomic era, as many scientists were investigating the effects of nuclear radiation on the lung cells of rats.
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Per usual, curiosity drove Herzenberg to Los Alamos. While there, he convinced the team that had developed the "volume sorters" to lend him blueprints. Herzenberg, a Biochemist by training, understood the need for interdisciplinary collaboration in order to develop this device into a cross-functional cell sorter. With the addition of a laser, a droplet technique borrowed from the ink-jet printer, and electrostatic charging, the team cobbled together the first FACS instrument by 1971.
Diagram of FACS
At this time, the only antibodies available to scientists were polyclonal and were highly variable leading to very inconsistent results. Herzenberg understood that the value of FACS hinged on a labeling mechanism that was both consistent and repeatable. Polyclonal antibodies lacked the specificity and reproducibility Leonard's new tool demanded. Luckily at that time, Herzenberg was collaborating with César Milstein and Georges J. F. Köhler at Cambridge, who were developing a mechanism to fuse a B cell to a myeloma cell which came to be known as a hybridoma. This "marriage" allowed for the continued production of an antibody that would only recognize a singular epitope.
Diagram of Hybridoma Development
The creation of these monoclonal antibodies acted as the backbone for FACS and provided the necessary specificity to fuel FACS into the clinical research field. As such, Herzenberg was able to identify and characterize the T and B lymphocytes in the mammalian immune system through FACS-based detection. Leonard understood the importance of this technology and readily shared both his expertise and cell lines and tools with the scientific community.

Leonard's Tesla-like approach, which valued knowledge and discovery over profit, spurred researchers and biotech companies alike.

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Unfortunately in October of 2013, Herzenberg passed away. He left behind a legacy of FACS and his valuable work on CD4+ T cells, which is still in clinical use to this day. In light of his major scientific contributions, BioLegend honors Leonard through an annual American Association of Immunologists award.

  1. PNAS Biography
  2. Stanford's Faculty Biography
  3. Leonard Herzenberg's Wikipedia page
  4. Wikipedia FACS Diagram
  5. Flow Chart Hybridoma
Contributed by Sean Cosgriff.
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