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80   DNA Breakthrough Points
     Way to Therapy by Virus
     The Washington Post   Saturday, January 13, 1968

     Planning for social progress demands a vigilant search for the
opportunity to link effective means with deserving goals.  We are rid-
den with problems against which we are simply too ignorant to mount a
frontal attack, for example, how to temper the ravages of aging.  In
such an area we must content ourselves with piecemeal advances in 
isolated sectors and work patiently to strengthen the whole framework of
human understanding.

     In the course of this process of basic research, opportunities
often arise where least expected.  Each should provoke the question,
"What can now be done that was not possible before?"  This is an
opportunistic search for newly answerable problems, but in the most
difficult and most important areas we have no way to program 
fundamental discovery.

     The replication of DNA in the test tube opens the way to a number
of new approaches to the study and treatment of disease.  It is 
virtually certain that, in the long run, our mastery of cancer and of 
senility will be reached with the help of this stepping stone.

     Meanwhile, there are some very concrete advances that we can map
out with existing insights.  For the moment, these would be most 
relevant to diseases that are connected with a hereditary defect and 
that have a simple biochemical basis.

     The plan is founded on an unlikely combination of biological 
studies ranging from the genetics of bacteria to virus-induced warts in
rabbits and the recent advances in molecular biology. It is a scheme
that we might call "virogenic therapy."  This is an extension of the
already well-founded use of tempered live viruses as vaccines to 
stimulate immunity against their wild cousins. To see the analogy we
must, however, focus on the earliest steps of a vaccination, since
the later step of provoking immunity is just one special case of 
virogenic therapy.

     In its essentials, a virus particle is a large DNA molecule  
protected by a protein coat. (For precision, we have to note that some
viruses are RNA, but the basic principles are the same.)  The DNA
codes for the production of a number of special proteins related to
the survival of the virus, including that coat protein but also 
including a number of new enzymes.

     The infection of a cell by a virus is therefore tantamount to
adding some new genes to that cell.  The consequences depend on the
specific quality of the virus as it has evolved in nature or been
contrived in the laboratory.  It may kill the cell and ultimately 
the whole animal.  Alternatively, it may be essentially innocuous,
adding a few additional proteins to the long list of those already
synthesized by the cell.

     In this context, the purpose of vaccination is seen to be to 
provoke the further synthesis of the virus's own coat protein.  This in
turn will provoke the host to develop immunity against that coat and
enable the host to recognize and destroy further incursions by the
same virus or its virulent cousins.

     Dr. Stanfield Rogers of the Oak Ridge National Laboratories has
pointed out that we should find viruses that code for other proteins 
needed by a giving patient, for example, insulin by a diabetic or the
phemylalanine-oxidizing enzymes by a PKU-infant.

     Such viruses might be found by a massive screening program to
test the enormous variety of viruses that continuously evolve in 
nature.  This kind of approach paid off very well in finding the 
antibiotics like streptomycin.  The odds of finding an insulin-coding 
virus are obviously rather slim, but such a program would justify 
itself anyhow with its by-product of encyclopedic knowledge of 
virus-cell biochemistry.  (That encyclopedia might one day save the 
humanspecies from extinction under attack by a virulent mutant of some 
now harmless obscure virus.)

     An even more aggressive approach is based on recent work like
that of Kornberg and Khorana on the enzymatic and chemical manipulation
of DNA.  It would be fanciful now to think of synthesizing an
entire viral DNA according to our intended design, which, anyhow, we
still do not know in sufficient detail.  We can, however, think of
extracting the DNA molecules that code, say, for insulin and chemically
grafting these to the DNA of an existing tempered virus.  These
new hybrid viruses would then have to be very carefully studied, and
perhaps modified even further, to select those appropriate for 
virogenic  therapy in man.

     This program needs to be discussed in a newspaper column as well
as in scientific journals because its success is mainly a question of
public policy.  Existing institutions are not well suited in either
style or scope to the innovative development side of "R.& D." for
health.

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