Biomedical Engineering Reference
In-Depth Information
microscope and an increasing capacity to interpret gross tissue changes, Joseph
Claude Anselme Recamier (1829) and Robert Remak (1854) both reported that
cancer tissue looked like embryonic tissue. These observations resulted in a new
theory, namely, that cancer arises from embryonic cells that persist in the adult.
This was formalized as the embryonal rest theory of cancer by F. Durante
(1874) and Julius Cohnheim (Cohnheim and Congenitales, 1875). According to
the embryonal rest theory, cancers grow out from small collections of embry-
onal cells that persist and do not differentiate into mature tissues in the adult.
The embryonal theory of cancer thus served as a precursor to the stem cell
theory of cancer as we know it today. However, during the last half of the 19th
century, the embryonal rest theory of cancer fell out of favor, to be replaced by
the de-differentiation theory of cancer (Sell, in press).
1.2.2 De-differentiation Theory of Cancer
In the latter half of the 19th century, there was an ongoing debate between those
favoring the embryonal rest theory and those championing the de-differentia-
tion theory of the origin of cancer (Bainbridge, 1914). The well-known surgeon
and pathologist, Sir James Paget, wrote in 1853 that cancers came frommorbid
material in the blood, essentially a variation of the black bile theory (Paget,
1853). Even Rudolf Virchow, the ''father of pathology,'' who described embryo-
nic tissues in teratocarcinoma, concluded that cancers arose from connective
tissue during chronic inflammation (Virchow, 1863). (Cohnheim was a student
of Virchow.) The earlier observation by Sir Percival Pott, considered to be one
of the first cancer epidemiologists, that chimney sweeps developed cancer of the
scrotum (Pott, 1775; Potter, 1963) was interpreted to mean that cancers were
due to de-differentiation of mature epithelial tissues induced by chemicals.
Others proposed a ''disequilibrium'' between connective tissue and epithelium
(Thiersch, 1865), a changed ''habit of growth'' of normal cells (Benecke, 1892
1893-; Adami, 1909), or the loss of ''restraining influences'' of the body on
displaced tissue cells leading to de-differentiation of mature cells (Rippert,
1904). Cancer was believed by Amedee Borrel (1907) and a number of other
scientists to be caused by infectious parasites. Later, Peyton Rous identified the
Rous sarcoma virus as a cause of cancer in fowl (Rous, 1911). Subsequently,
virus infections of stem cells, such as by human papilloma viruses, have been
demonstrated to be a cause of some epithelial cancers. In squamous cell carci-
noma of the uterine cervix associated with human papilloma virus infection, the
initially infected and transformed cell is the basal stem cell, but productive
infection requires keratinocyte differentiation (Munger and Howley, 2002;
Garland, 2002). Finally, in 1914, sea urchin cells embryos were found by
Theodore Boveri to have an abnormal chromosome composition, and it
was concluded that genetic changes in mature tissue cells cause cancer via
de-differentiation (Boveri, 1914). The cumulative impact of these observations
lent little support to the embryonal rest theory of cancer. By 1914, William
Seaman Bainbridge,
in his authoritative topic ''The Cancer Problem''
