From the World of Modern Cell Science, A Long and Sorted Coming-of-Age Story

By David Brown
Washington Post Staff Writer
Monday, April 7, 2008

Learning to tell things apart and sort them into different piles is a key cognitive milestone of early childhood. It's probably not a surprise that the skill comes in handy all through life and in all manner of activities.

In biology, sorting and piling is the essential first task for studying the differences between things that are, in most ways, similar to each other. People have done that with whole organisms -- beetles, mushrooms, mice -- for thousands of years.

Only in the past 50 years, however, have people been able to perform the task on the building blocks of life, namely cells.

That capability, achieved through devices called cell sorters and flow cytometers, has turned out to be one of science's great technological advances. With unprecedented insights on the molecular basis of disease and the rise of "personalized medicine," cell sorting is heading into its golden age.

Some forms of high-speed cellular identification and sorting are used to do CD4-cell counts in patients infected with the AIDS virus; in diagnosing leukemia and lymphoma; and in helping physicians decide what drug may best treat certain types of cancer. The technology is also used for innumerable tasks that have not yet gotten to the clinic, the best-known being the isolation of stem cells from blood and amniotic fluid.

In some cases, identifying and counting the cells is the work to be done. At other times, the cells must also be physically separated and captured for future use.

Finding and sorting a few cells from a great mass of them is sometimes likened to finding a needle in a haystack. But the job is more like watching a parade of 10,000 undertakers, spotting the two who are wearing yellow ties and the three wearing pink ones, and then getting them out of the line without making everyone else lose step.

How a machine capable of doing that came about is a story that entails all the forces of science: brains, work, timely observation and intellectual cross-fertilization.

The ancestral device was a machine for counting blood cells developed by an engineer named Wallace H. Coulter in 1949.

The principle: If a stream of cells traveling single file in salt water was sent through a tiny orifice and an electric current was directed across the opening, the cells could be distinguished by size based on how much they impeded the current. The Coulter Counter, patented in 1953, is still used today in hospitals to count red cells, lymphocytes, monocytes and other cells in blood.

Figuring out how to sort cells once they were detected was the accomplishment of a physicist named Mack J. Fulwyler.

He was working at Los Alamos National Laboratory in New Mexico on ways to measure radioactive fallout when the atmospheric nuclear test-ban treaty of 1963 suddenly lightened his workload. He began to help biologists at the lab and took up the problem of isolating different types of cells.

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