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61   Science Trails Vaccine Against
     Undiagnosed Viral Infections
     The Washington Post, Saturday, September 9, 1967

     The chemotherapy of virus disease is one of the most urgent
challenges to medical research.  In contrast to the large arsenal
of chemical weapons at our disposal for combatting bacterial
infections, we have no comparable battery to use against viruses.
So preventive vaccination remains the most effective defense, and
a very limited one for many important diseases.

     Vaccination is used to provoke the human body to produce specific
antibodies capable of neutralizing free virus particles before they
have been widely entrenched in cells.  If the infection has already
become entrenched, the antibodies have very little useful impact on
it.  Furthermore, we don't know how to make safe and effective vaccine
for use against many viruses.

     Thus researchers have long been interested in less specific
antiviral agents.  These would allow therapy to begin against many
viral infections before a specific diagnosis was made -- a process
that would often take much too long in relation to the time course of
the infection.

     The discovery by Dr. Alick Isaacs of interferon, and its further
characterization as a protein with a broad range of virus-inhibitory
action, is one of the most promising avenues of current research in
this field.

     It had long been known that a cell infected with one virus would
not readily sustain the growth of another.  This can now be
attributable, in mammalian cells, partly to the production of the
interferon protein in response to the first infection.  Dr. Isaacs
reasoned that relatively innocuous viruses might be purposely
introduced to stimulate the production of interferon, or else that
interferon might be purified from animal tissues for clinical use
in man.

     Interferon has had promising effects on experimental viral
infections, but some hopes for its wide use were dashed by the finding
that interferon from one species would not work except in cells of the
same or closely related species.  No practical way to produce human
interferon in clinically useful quantities is apparent.

     Ultimately, it may be possible to synthesize it, but we are
still some way from handling the synthesis of proteins of interferon's
rather large size (molecular weight 70,000 compared to 5734 for
insulin, which has been synthesized).

     Virologists have, then, turned to agents that might behave like
viruses in inducing treated cells to synthesize their own interferon.

     A research team from the Merck Institute for Therapeutic Research
recently reported that certain types of RNA (ribonucleic acid) were
efficient interferon-inducers.  It was an intellectually satisfying
insight that these RNA's resembled those of certain viruses in
displaying a double-stranded structure, usually associated with DNA
rather than RNA, in normal cell constituents.  In fact one of these
inducers had already been described as an antiviral agent named
helenine, and only now is proven to be an RNA.

     These reports seemed to point to one of the first practical
applications of a nucleic acid in medicine, apart from the
extraordinary conceptual impact of our knowledge of RNA and DNA.

     Other interferon-inducers have, however, been reported that show
a much wider basis for doing so.  In particular, Dr. Thomas Merigan
at Stanford University has shown that there is such activity in
synthetic polymeric acids which have a much simpler structure than
nucleic acids.  These compounds have certain disadvantages;
particularly, they are too stable and therefore are not rapidly
eliminated from the body.  Further research is in progress, however.

     While these approaches may give us useful, expedient drugs, the
most important long-term benefits will derive from understanding
how interferon modifies the cell to inhibit virus growth, and yet
leave the cell still able to use its proper RNA and DNA for healthy
pursuits.

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