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    The Washington Post, Sunday, March 5, 1967

     Vaccination was introduced into medical practice by Jenner's
use of cowpox as a preventive against smallpox.  It has since become
one of the major triumphs of medicine.  Founded on this blind
empiricism, the procedure has been extended to a great many other
diseases by the application of a new science of virology.  In fact,
vaccination is the only important way we now have to cope with virus
infections, such as smallpox, polio, rabies, yellow fever, influenza
and measles.

     We see on the horizon vaccines for rubella (German measles), 
mumps and chickenpox.  The possibility that some tumors may be caused
by viruses is still a conjecture based on animal experimentation, but
if it can be substantiated it will point to the chance to develop
vaccines against the corresponding viruses.

     The vaccine usually works by provoking the inoculated host to
make antibodies.  These are modified globulin proteins capable of
recognizing and neutralizing virus particles while they are in the
bloodstream and other body fluids in transit from an infected cell
to a fresh one.  The antibody reaction is extremely specific.  Hence
the vaccine must contain particles closely similar to those causing
the disease.

     Modified viruses of two kinds are used: chemically altered
particles ("killed viruses") unable to propagate in the host, and
genetic mutant virus strains ("attenuated viruses") which are still
capable of limited propagation, but whose biological properties are
altered to prevent serious disease after their artificial introduction
into the host organism.

     Killed vaccines must usually be injected to enable them to reach
the antibody-forming tissues.  Attenuated viruses can often be taken
by mouth and, in view of their own propagation, in much smaller
doses.  Furthermore, their persistence in the body usually leads to
a much longer immunity, sometimes for an indefinite period.

     Attenuated viruses are therefore cheaper than killed viruses --
both to administer, because no injection is needed, and to prepare,
because there is less virus per dose and less attention must be paid
to chemical modification.

     The Salk polio vaccine is the best known example of a killed 
vaccine.  Virulent poliovirus is killed with formaldehyde.  Sabin
polio vaccine is a live attenuated vaccine which uses carefully
selected strains of poliovirus.

     The development of a vaccine then goes through three principal
phases 1) the close study of a disease and the successful isolation
of a causative virus 2) the development of practical techniques to
produce the virus on a large scale and an assay of it and 3) the 
discovery of reliable modifications, either chemical inactivation
or an attenuated mutant strain.  The third phase still raises many
scientific questions in spite of its empirical success so far.

     Salk's procedure of formaldehyde-inactivation demanded the
most meticulous attention for reliable results.

     Attenuated mutants are equally empirical, with the possibility
always remaining that virulence might return under odd conditions --
like unexpected routes of attack, or weakening of the host by disease,
or malnutrition or concurrent drug therapy.

     Any complacency we might have had about the foundations of
virology was badly shaken by our experience with polio vaccination
in the last decade.  Overall, this was a triumph.

     As was learned only five years later, starting in 1955 many
millions of children who were inoculated with polio vaccines also
received a contaminating virus, SV-40, derived from the monkey
tissues on which the virus was grown.  This virus has not subsequently
been proven to exert any harmful effect.  It was the purest good
fortune that this was not the worst medical catastrophe in history.
SV-40 virus is known to be able to cause tumors when injected into
newborn hamsters, and can be detected by effects on tissue cultures
of cells from many species, including man.

     Virology is still too primitive to give absolute assurance
against the repetition of such incidents, or others we still are too
ignorant to ask about.  We can ill afford not to make utmost practical
use of empirical vaccines.  However, we will be severely punished
in the long run if we do not sharpen our vision -- down to the
molecular level -- in our use of these agents.

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