In 1965, Stanley Gartler and collaborator David Linder were able to demonstrate clonality of tumors in human females using an event (
X chromosome inactivation) that occurs early in development in mammalian females. X chromosome inactivation randomly silences most of the genes on one of the two X chromosomes in every cell of the
embryo. The female thus becomes a
mosaic for any
X-linked gene for which she is
heterozygous, and normal tissues are consequently composed of a nearly equal mixture of cells expressing the two different
phenotypes. Gartler reasoned that, if a tumor begins from a single cell, then all the cells of that tumor should express the same, single X-linked allele. By examining expression of different
isoenzymes of the
sex-linked glucose-6-phosphate dehydrogenase (G6PD) locus in heterozygous women, Gartler and Linder demonstrated that
leiomyoma tumor cells, even those from cancers consisting of billions of cells, expressed only one form of the marker, whereas even small patches of normal tissue contained cells expressing both forms of the marker. This finding was consistent with the growth of a single founder cell into a tumor. The clonal origin of various tumors has been confirmed many times since, both initially through Gartler's work with a junior colleague, Philip J. Fialkow, and by other groups. In 1967, Gartler became interested in establishing a system for studying human genetics in somatic
cell culture. He initially studied eighteen (supposedly) independently derived established human cell lines obtained from the
American Type Culture Collection, including
HeLa. Examining
isoenzymes, he typed them for a number of genetic polymorphisms, including the X-linked
G6PD variant. The cell lines turned out to be genetically identical, and moreover, all carried the G6PD allele found almost exclusively in people of African descent. HeLa, which was the first successfully established human cell line, was derived from a woman of African descent named
Henrietta Lacks, so this result suggested that the cell lines were not truly independent, but had instead been contaminated by HeLa cells. It was not realized at the time that nearly all attempts to establish human cell cultures resulted in cell lines with
limited life spans. Dr.
George Gey, the originator of HeLa, had sent those cells to all who requested them, and the contamination problem arose because many workers were growing the immortal HeLa cell and mortal human cell strains in close proximity. Since the use of genetic markers to characterize and distinguish cell lines at the time was virtually non-existent, contamination events from HeLa went undetected. In spite of the evidence, initially, the idea of laboratory errors leading to cross culture contamination was not universally accepted: an alternative explanation was that, when cultures became established, their G6PD phenotype changed. Gartler's original paper to
Nature went to lengths to dismiss this possibility, surveying over 100 tumors to see if there was a phenotypic change in either G6PD or
PGM, as well as trying other experimental approaches to test the idea. He concluded that "all evidence seems to point to the stability of the G6PD and PGM phenotypes both
in vivo and
in vitro." demonstrating the association between
fragile X syndrome and delayed replication of
FMR1, and identification of
DNMT3B as the gene underlying
Immunodeficiency–centromeric instability–facial anomalies syndrome, the first recognized human hypomethylation disease. In 1991, evolutionary biologist
Leigh Van Valen put forth an argument that the HeLa cell line constituted a new microbial species, which he proposed be designated
Helacyton gartleri, in recognition of Gartler's work. ==Honors==