100 years of sperm chemotaxis

Exactly 100 years ago, F.R. Lillie reported chemotaxis in animal sperm for the first time (Lillie, 1912). Chemo-taxis refers to the directed movement of a cell or organism to the source of a chemical gradient; the chemical agent that elicits this movement is called a chemoattrac-tant. Chemotaxis had previously been shown by Pfeffer (1884) for fern spermatozoids; however, attempts to demonstrate chemotaxis in animal sperm had failed. Lillie was an eminent scientist of the time; he was professor of embryology at the University of Chicago, president of the National Academy of Sciences of the USA, and a towering figure of the scientific community at the Marine Biological Laboratory (MBL) in Woods Hole, MA. From 1908 to 1925, he served as director of the MBL. In a report entitled " The production of sperm iso-agglutinins by ova " (Lillie, 1912), Lillie described an agglutination reaction when drops of seawater that had been conditioned with unfertilized eggs were injected into a milky suspension of sperm from the sea urchin Arbacia punctulata. The sperm agglutinated—or clumped—into small masses, or beads. The reaction was reversible; after some time, the sperm freed themselves and regained full mobility. Lillie called the ova-derived factor an iso-agglutinin because it acted on sperm of the same species. Because Lillie thought that the iso-agglutinin represented a key factor for fertilization , he dubbed it " fertilizin " (Lillie, 1913). Lillie interpreted the agglutination as physical cross-linking of sperm by egg jelly molecules analogous to the antigen– antibody reaction. The spontaneous reversal was later explained by fragmentation of fertilizin by a sperm enzyme called " lysin " (Tyler, 1941). At the end of his manuscript (Lillie, 1912), Lillie reported almost in passing that egg extracts also contain a chemotactically active agent distinct from the iso-agglu-tinin. The short passage about the chemotactic behavior is worth quoting for its clarity and succinct style: " The egg-extracts contain not only an agglutinin for the spermatozoa, but also an aggregative agent, i.e., a substance towards which the spermatozoa are positively chemotactic. This may be readily demonstrated by the form of the reaction when a drop of the fluid to be tested is injected into a sperm suspension beneath a raised cover glass. If an aggregative agent be present, a ring of spermatozoa forms at or within the margin of Correspondence to U.B. Kaupp: u. b. k a u p p @ c a e s …