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101   That 'Academic' Work on DNA
      Applied to a Human Disease
      The Washington Post, Saturday, June 8, 1968

     Excitement about the new biology of DNA has tended to provoke
either of two reactions: that little men would soon be synthesized and
come swarming out of the laboratories or that the whole study of
molecular biology was mainly of academic importance and we would see
little practical impact of it within our lifetime.

     More sensible observers have suggested that we would see ever
deeper insight into cancer and other cell pathology over the coming
years and decades.  It is gratifying, and a little surprising, to
see how quickly a concrete application of DNA enzymology has arisen in
relation to a human disease.

     DNA, or deoxyribonucleic acid, is the substance within the cells
that controls heredity.

     Xeroderma pigmentosum is a rare disease which once occupied a
prominent place in the textbooks mainly because its gene was wrongly
located on the sex chromosome.  In fact, it now seems that the
Xeroderma gene is located on the same chromosome as the ABO blood
group factors.  In addition, most of the diagnosed cases belong to
the O blood group, which speaks for some developmental association
of the disease with the O group factors.

     The principal manifestation of Xeroderma is the sensitivity of
the skin to sunlight, specifically to ultraviolet light.  Besides
excessive "sunburn damage", the patients also have a very high
liability to cancers of the skin and to malignant melanoma.

     Cases in which 20 tumors have been removed are not unusual and 
most die from their cancers at an early age.  The main interest of
the disease to medical science, in view of its rarity, is the light
it can throw on the biology of cancer, and on freckles, and possibly
on relationships between them.

     Dr. J. E. Cleaver of the Radiobiology Laboratory, University of
California Medical Center, San Francisco, reported remarkable findings
on cultured skin cells from Xeroderma patients in the May 18 issue of
Nature magazine.  The DNA of cell nuclei is vulnerable to chemical
damage by ultraviolet light, which introduces "thymine dimers" into
the normal DNA structure.  These abnormal linkages interfere with
the fundamental genetic functions of the DNA molecule and, unless
repaired, either kill the cell or introduce mutations into the next
generation of DNA.

     Most organisms, as an adaptation to living on a sun-baked earth,
have developed protective pigments to shade their DNA and have also
evolved biochemical repair mechanisms to eliminate thymine dimers
when they occur.  The repair generally involves three steps, each
requiring a different enzyme: (1) the recognition and excision of
thymine-dimer segments from the DNA; (2) synthesis of patching copies
(repair replication) from the alternative strand of the DNA, and (3)
healing in the patched segment.

     The biochemical research on DNA repair is closely related to the
recent success in replicating a bacterial virus.  Nothing could be
more academic, nor seemingly more distant from human affairs, than
the genetic studies of sex in bacteria that also underlie much of
this kind of work, and which have made sporadic entertainment for
Congressmen poking fun at research.

     Dr. Cleaver reported that Xeroderma cells are defective in the
process of DNA repair after ultraviolet damage.  Further work is in
progress to determine which of the essential enzymes is altered in the
cells from the Xeroderma patients.  The process of DNA repair is
obviously an essential part of our inherent biological resistance to
cancer, with which we dispense only at our peril.

     This work exemplifies the excellent biomedical research at our
universities, supported by agencies like the Atomic Energy Commission,
the National Institutes of Health and the National Science Foundation.
Its further growth, however, is being strangled in the budgetary
crunch between the President and Congress.  It is no consolation that
their children will share in paying the price of their neglect.

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