Genetics Prof. Len Herzenberg accepted the Kyoto Prize last month for his contributions to biotechnology, including his pivotal role in developing the Fluorescence-Activated Cell Sorter (FACS) machine that has transformed both the research and medicine.

“Yes, it was a surprise,” said Herzenberg, who was visited by representatives of the Inamori Foundation — the body which funds the Kyoto Prize and oversees naming of its recipients — last May. The award was announced a month later.

“I asked them how many candidates there were, but they wouldn’t say,” recalled Herzenberg of the May visit. “It was only later that I learned there were three candidates for three prizes!”

The Kyoto Prize was established in 1984 by Japanese businessman and ceramics engineer Kazuo Inamori. Modeled after the Nobel Prize, the Kyoto Prize was designed “to honor people who have made extraordinary contributions to science, civilization, and spirituality.” The Inamori Foundation gives awards annually in each of three categories: advanced technology (including biotechnology, engineering and information science), basic sciences, and arts and philosophy.

Though the Kyoto is often compared to the Nobel in terms of prestige and significance, it should come as no surprise that Herzenberg, teaching at Stanford since 1959, is a laureate. Since its inventions nearly 40 years ago, the FACS has become ubiquitous in research labs and clinical settings and played part in everything from stem cell research to leukemia and AIDS diagnosis.

“The FACS has been used pretty broadly in mouse as well as human immunology,” Herzenberg said. “But the applications have been much broader than immunology; the FACS is used in almost all of cell biology and medicine.”

The FACS machine sorts single cells based on their fluorescent properties: cells can be treated with antibodies tagged with a colored fluorochrome since the antibodies only bind to a specific protein of interest. Inside the machine, cells are suspended in a stream surrounded by sheath fluid, which races past a laser at a rate of 5,000 to 10,000 cells per second. The stream breaks into tens of thousands of drops, which are charged and then sorted. The laser detects fluorescence and translates its readouts to a computer, which charges the drops, after which charged plates shuttle cells into the appropriate bin.

Herzenberg developed the very first FACS machine in 1969, combining biology with technology developed at Los Alamos National Laboratories for sorting small particles — in particular, fallout from atomic-bomb testing — based on size. The first commercial FACS machine was released in collaboration with the company Becton-Dickinson (BD). Another important milestone in the development of the FACS was the use of monoclonal antibodies, which are antibodies made from “hybridomas,” or B-cells that have been “immortalized” by fusing with a cancer cell. Compared to traditional polyclonal antibodies, monoclonal antibodies are much more specific and extremely useful. Herzenberg is credited with making fluorochrome-labeled monoclonal antibodies widely available to scientists, in a system whereby scientists who developed monoclonal antibodies turned them over to BD for labeling, and BD would then continue to manufacture the antibody for general sale.

“Prior to monoclonal antibodies, everyone had to make their own antibodies in small amounts,” Herzenberg said. “My wife and I felt that it would be a great boon for everyone to have the same antibodies as everyone else. Using this method, we could distribute the antibodies very widely as well as make the company a profit. Using the marketplace was better than rationing, which hadn’t worked because different scientists need very different amounts of antibody depending on the type of research they were doing.”

The FACS machine has continually evolved. Over the years, the number of available color labels has increased exponentially as researchers have isolated more of these markers from algae and other sources. Jellyfish genes can be incorporated into a cell’s DNA and are frequently used to sort cells with the FACS. The Herzenberg lab also continues to hone FACS technology, with the development of machines that can read several colors simultaneously and new ways to process FACS data.

In addition to improving upon the FACS’s capabilities itself, Herzenberg’s lab has applied the FACS in diverse areas. For example, they have recently used the FACS to investigate the role of white blood cells in cystic fibrosis — research of which has resulted in Phase II trials for treatment of the disease.

Herzenberg also emphasized the use of FACS for diagnosing and monitoring progress in patients of AIDS, the severity of which is gauged by the patient’s level of an immune cell called the helper T-cell.

“We are working on developing an inexpensive flow cytometer to be used in the field, such as in Africa and poor countries in Asia, to be used for diagnosis or tracking progress of HIV treatment, if treatment is available,” Herzenberg said.

Herzenberg’s humanitarian accomplishments include some closer to home as well. In May, he recalled, the visiting Inamori Foundation representatives spoke at length to him about a project he and his wife, Genetics Prof. Lee Herzenberg, initiated to encourage low-income students from East Palo Alto to pursue higher education.

“I learned that the Kyoto Prize was not just for scientific accomplishment,” he said. “There were also looking for humanitarian accomplishments and interests.”

Herzenberg described the program for black high school students from Ravenwood High as an enrichment and educational experience.

“We brought in someone from the College Board, some faculty and some students to talk to them, and took them out to restaurants, the theater, movies, around campus and to labs,” he said. “They’d never been west of the freeway. It was an absolutely new experience for them.”

Later, the Herzenbergs organized SAT tutoring and college counseling for the students. The program continued for years, during which time many of the students did indeed go to college — from a high school in which only one student had ever succeeded in doing so, on a basketball scholarship. Herzenberg later headed a committee for promoting diversity in the medical school.

Speaking from an armchair in his office, his pet poodle at his side, Herzenberg still expresses wonder at the FACS’s enduring impact.

“It’s remarkable that a high tech-field can be basically the same some 35 years later,” he said. “It’s like an airplane: it might have changed some, but you still have the wings, the propeller. With the FACS, it’s still the basic idea of getting cells into droplets that get charged and then sorted.”