LIVE POLIO IRUS VACCINES

Discussion
87
Dr. Koprowski's statement at the first session
that their importance should not be exaggerated.
However, in view of the possible presence
of viruses, such as the "B" virus and
measles virus, it is important to eliminate these
viruses if that can be done, and it can be done
to some extent by using cultures from single
monkeys as lots.
It has also been found that treatment of the
suspensions with chloroform and with ether will
destroy the activity of the foamy agent, the
measles agent, and "B" virus. Of course, it
does not eliminate the polio-like viruses, the
ECHO viruses, or the adenoviruses, or, in this
particular case, the virus that Dr. Hilleman has
described.
I should emphasize that one should not assume
that these viruses are harmless. One
should take every precaution to eliminate them
or to prove that they are harmless before presuming
that they are.
DR. MURRAY: Dr. Hilleman provided our
laboratory with some materials in connection
with his vacuolating agent. Dr. Baron has actually
been carrying out this work personally
and can answer questions concerning any of the
details. However, I would say that, short of
actual neutralization tests, we have been able
to confirm the results that Dr. Hilleman has
presented.
In this respect, I would say that we were fortunate
in having in stock a number of vervet
monkeys which were kindly supplied to us by
Dr. Gear some years ago. Otherwise, we would
not have been able to carry this out.
To digress for a moment on the question of
eliminating some of these agents, I was interested
in Dr. Gear's remarks and would like
to mention, in case some of you did not pick
this up, that recently Dr. Hiatt of our Division
has carried out some work on the differential
destruction, particularly of B-virus, using the
phenomenon of the photodynamic action of certain
dyes. This seems to be quite successful, at
least from the point of view of reducing the
titer of B-virus, without simultaneously reducing
the titer of the poliovirus component of
the virus fluids.
DR. DULUBCCO: In view of what has been
said about the presence of these viruses and
the implications of the many kinds they can
have, I wonder whether those who make the
vaccine should not consider purifying the virus.
With modern technology, I believe, purification
could, without tremendous effort, be
achieved by a combination of various types of
chromatography and equilibrium density gradient
sedimentation.
In fact, poliovirus happens to be probably one
of the animal viruses of highest density. By
equilibrium density gradient sedimentation one
could remove essentially everything except the
polio-like viruses which, from what we heard
at the first session, could be separated by chromatography.
DR. SABIN: I think that a little history on
the 10 sera that I sent to Dr. Hilleman may
be of interest. Five of the sera were from
children who had no Salk vaccine and five from
triple-negative children who were fed the three
types of vaccine seriatim-first in 1957 and then
in 1959. After the initial feedings, poliovirus
predominated, and if this other virus could multiply
in man it might conceivably have been
suppressed.
But the second series of feedings, which were
carried out two years later, three in a row,
were not associated with multiplication of poliovirus
in the intestinal tract and presumably this
virus should have had a clear field for multiplying-if
it possesses the capacity to multiply
in the human intestinal tract.
Accordingly, the absence of any neutralizing
antibodies in the sera of these five children is
an indication that there was not sufficient multiplication
to produce antibodies. The stools of
all these children were preserved, and we prepared
to test them for evidence of actual multiplication
in vervet monkey-kidney cells.
But until recently, Dr. Hilleman was misinformed
about the type of monkey he was dealing
with. He had told us to get vervet monkeys,
then he telephoned a short time ago and said
the monkeys he was working with were not vervets
but grivets.
I have heard Dr. Murray speak of having
obtained the Hilleman virus effect in cultures
from monkeys which he calls vervets. Perhaps
this virus is also pathogenic for vervet monkeykidney
cultures. The difference, according to
Dr. Hilleman, is that the vervets come from