Restriction endonucleases are enzymes which attack and digest bacteriophage DNA, but do not do this to the host cell.

Host cell DNA is protected, since these or other enzymes can modify it by adding methyl groups to a nucleotide within the recognition sequence.  This is called process is called methylation.

In 1970, Hamilton Smith and Kent Wilcox discovered that the restriction enzyme HindII (produced by Haemophilus influenzae) cleaves in a predictable way within its recognition sequence, but does not modify host DNA.

Daniel Nathans used HindII to cut simian virus 40 (SV40) into small portions called restriction fragments, which could then be separated by gel electrophoresis.  He then deduced the order of the fragments and their corresponding restriction sites to produce the first restriction map.