LIVE POLIO IRUS VACCINES

DISCUSSION
CHAIRMAN ANDERSON: There are two more
papers this morning dealing with markers, and
one the first thing this afternoon, so I am
certain there will be discussion that revolves
around all four of these papers.
Are there any comments at this time? This
does not preclude coming back later for further
discussion, after the other papers have also
been presented.
DR. SABIN: The data that Dr. Melnick has
presented are not new data. We have known
for several years-and many people have demonstrated
it before-of the changes in the viral
population that occur after multiplication in the
intestinal tract.
As regards these changes with the strains that
I developed, it has previously been reported by
myself and others that they are greater for
Type 3 than they are for Type 1 and Type 2.
This Dr. Melnick has again very nicely shown
by indicating, for example, that he had in his
studies no rct/40+ cultures of excreted virus
after administration of Type 1 and Type 2, but
a considerable number of such cultures of
Type 3.
I have previously reported similar findings,
although I did find, in testing a larger number
of specimens, that occasionally also in the case
of Type 2, after a long period of multiplication,
one may get a culture that has increased capacity
to multiply at 400 C.
The most important thing that has come out
in our studies on Type 3 is that this change
in the capacity to multiply at 40 ° C. seems to be
acquired rather rapidly after multiplication in
the intestinal tract, within a few days.
Furthermore, this property may not be present
at all in the original stool, but may come out
after a single propagation at 360 C. in monkeykidney
tissue culture.
I think that, in speaking of changes in viral
progeny, it is important to keep in mind not only
the changes that one finds in the culture, but
also quantitative aspects. I believe that anyone
who thinks in terms of viral genetics must
think in terms of quantitative aspects of the
property in the population of virus particles.
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It is evident that the whole population of virus
particles does not undergo a change. Therefore
one must pay attention to the proportion
of viral progeny that changes, which may then
be selected either in the tissue culture or the
monkey.
When studies are carried out on the original
stool specimens, one can show that only 1 per
cent or less of the viral particles may be involved
in a given change. Therefore, even
when one inoculates 60 tissue-culture doses
intraspinally, a very sensitive place, it is potentially
possible to give advantage to those few
viral particles that have a greater capacity for
multiplication in these neurons.
The new data that Dr. Melnick has presented
on intramuscular inoculations, I think, again are
not a reflection of anything more than has been
observed before.
When you have a viral culture that has an
increased capacity for producing paralysis by
spinal inoculation, and one inoculates, as he
has done, 10 million to 100 million tissue-culture
doses intramuscularly, 1 know from previous
experience that that will lead to greater invasion
of the axis cylinders of the neurons which are
present in the muscles. The muscles contain
the processes of the anterior horns in the spinal
cord.
No one has ever criticized the results presented
by Dr. Melnick last year on the basis
of the traumatic changes produced in the spinal
cord. It was merely pointed out that if the virus
inoculum is artificially spread out over a larger
portion of the spinal cord, the incidence of
paralysis can be greater.
Now, with regard to the data on contacts of
children fed the Type 3 vaccine that Dr. Melnick
has presented, I have also tested those same
specimens, and the results may be seen in the
proceedings of last year's Conference. Dr. Melnick
has presented results only with one large
dose of virus, and I presented data with several
doses.
When the thing is done quantitatively, one
can show that the virus is still attenuated, because
with 100,000 TCD1 0 you get no effect.
There was a time when Dr. Melnick worked