LIVE POLIO IRUS VACCINES

DISCUSSION
CHAIRMAN BURNET: Thank you, Dr. Sabin.
Dr. Dulbecco.
DR. DULBECCO: I would like to ask Dr. Sabin
one question. He said that the culture as a whole
had both properties, multiplied at 25 and at 40.
Does this mean that individual plaque lines were
able to do so, or was the culture a mixture of the
two types, of which half were able to do one
thing and half the other, and therefore the culture
as a whole appeared to do both things?
DR. SABIN: The data that I reported involved
tests on the first-passage monkey-kidney culture
fluid. If you suggest the possibility that in those
culture fluids half of the virus particles were
made up of those that could multiply well at 250
C. and not at 400 C., while the other half of
particles that multipled well at 400 C. but not
at 250 C., one can only say that that may be
possible. Actually, in order to prove that a
single virus particle has both properties, the
tests would have to be carried out on purified
single plaque progeny.
CHAIRMAN BURNET: Are there any further
questions or comments?
DR. BODIAN: I think one should re-emphasize
Dr. Dulbecco's suggestion in interpreting
his very interesting data, namely, if there really
are a large number of particles which are capable
of growing at each temperature, we are saying
that it is possible with human passage to
quickly select very large proportions of new
virus. This would be another interpretation of
Dr. Sabin's data to add to the possibility he has
suggested.
DR. SABIN: Selection can occur predominantly
in the first-passage tissue culture. The original
stool may contain only 1 per cent or less of
virus particles capable of multiplying at 400
C., and then a single passage at 360 C. gives
these particular ones a selective advantage in
the final population. We always have to think
of this in quantitative terms. I think that a basis
for such a selective advantage was provided by
109
studies that Dr. Lwoff carried out. He showed
that virus particles that can multiply at 40 ° C.,
when grown at 360 C. to 370 C. produce progeny
more rapidly than viruses which cannot grow
well at 400 C.
So that starting off equally, the rct/40+ particles
can end up in the majority after a single
passage in tissue culture at 360 C.
I should like to add that we also found the
reverse here, just as we found with Type 3
viruses before, namely, that after a long continued
propagation in the same child, one may
end up with a virus population that is again
rct/ 40-.
DR. STUART-HARRIS: I should like to make
two brief comments. It seems to me that in comparison
with the data which we presented last
year, this year we have a good deal more information
concerning the properties of the
strains used as vaccines and also of the properties
of the strains recovered from children immunized
with vaccines. All of this information seems to
me to point in the same direction, namely, that
whatever particular property we study in relation
to these strains, we come up with something
which can only be described as a graded
characteristic.
I think that this is brought out in regard to
the T marker, of which we have heard so much,
that one has strains which vary in property over
quite a wide range, a point which I am certain
was emphasized before by Dr. Sabin when, in
the earlier studies on neurovirulence, he noted
that this, in fact, was a graded characteristic.
One did not just have virulent strains or nonvirulent
strains; one had a spectrum of this particular
property.
And it does make one feel, I think, that in this
particular virus, the poliovirus, one is dealing
with something which has infinite capacity for
variation. What the interpretation of that may
be I would not like to say. At any rate, it does
seem to me to be an extremely variable virus in
all these various ways.
My second comment is in regard to Professor
Zhdanov's remarks at the first session, when he