John A. Ryan, Ph.D.

Ross Granville Harrison

It was in 1907 while he was at Johns Hopkins University that Ross Harrison published a short but critical article (1) that successfully introduced a new technique, tissue culture, to settle the argument of how nerve fibers originated. Other scientists had examined cells in vitro before but none had successfully cultured and experimented with them (7). It was Harrison who first successfully overcame basic culture problems and created a technique others could follow.

Using expert surgical and aseptic technique developed from successfully operating on tiny frog embryos, Harrison explanted embryonic frog neural tube fragments into a drop of fresh frog lymph on a sterile coverslip. Once the lymph clotted, he inverted the coverslip over the well in a glass depression slide creating a hanging drop culture, a technique often used by microbiologists for studying bacteria. He then watched the development of frog nerve fibers in vitro (literally in glass) from the neurons in the explanted tissue. Thus he solved the basic cell culture problems of medium, culture vessel, observation and culture contamination (which he did encounter). Because they were relatively short term cultures he was not faced with the problems of feeding or subculturing his cultures.

To grow his tissue explants, Harrison adapted the hanging drop technique that microbiologists used to study live bacteria.

As he so clearly stated before the 23rd meeting of the Society for Experimental Biology and Medicine in that year in New York: "The immediate object of the following experiments was to obtain a method by which the end of a growing nerve could be brought under direct observation while alive, in order that a correct conception might be had regarding what takes place as the nerve fiber extends during embryonic development from the nerve center out to the periphery."

With this simple experiment cell culture began its journey to become both a major tool for research as well as the means of producing monoclonal antibodies, vaccines and cell-produced drugs worth many billions of dollars every year. His work stimulated many other researchers to begin using these techniques. Among the most notable were A. Carrel and M. Burrows at the Rockefeller Institute in New York City and who he helped train, W. Lewis and M. Lewis at the Carnegie Institution at Johns Hopkins in Baltimore, T. Strangeways and H. Fell in England, A. Fischer in Denmark, G. Levi in Italy, and L. Loeb in France. It was not a smooth road; many more breakthroughs were needed to get to where we are today. For additional information on the life and research of Ross Harrison, see the 1961 biography by M. Abercrombie (4) or the 2002 online article by Schiff (6).

Suggested Readings

1. Harrison, R. (1907) Observations on the living developing nerve fiber. Anat. Rec. 1:116-128; Proc. Soc. Exp. Med, N.Y. 140-143.
2. Harrison, R. (1910) The outgrowth of the nerve fiber as a mode of protoplasmic movement. J. Exp. Zool. 9:787-846.
3. Keshishian, H. (2004) Ross Harrison's "The Outgrowth of the Nerve Fiber as a Mode of Protoplasmic Movement" J. Exp. Zool. 301a:201–203.
4. Abercrombie, M. (1961) Ross Granville Harrison. 1870-1959. Biographical Memoirs of Fellows of the Royal Society. 7:110-126.
5. Harvey, A. M. (1975). Johns Hopkins--the birthplace of tissue culture: the story of Ross G. Harrison, Warren Y. Lewis, and George O. Gey. Johns Hopkins Med J 136(3): 142-149.
6. Schiff, J. A. (2002). Old Yale - An Unsung Hero of Medical Research. Yale Alumni Magazine http://www.yalealumnimagazine.com/issues/02_02/old_yale.html
7. Witkowski, J. A. (1983). Experimental pathology and the origins of tissue culture: Leo Loeb's contribution. Medical History, 1983, 27: 269-288. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1139336

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