LIVE POLIO IRUS VACCINES

Discussion
49
belonging to one gene, or approximately so.
We also know of only one protein and it is
not likely that there are many more, owing to
the structure and the compactness of the virus.
In work done recently at our Institute in
Pasadena, it was found that in bacterial viruses
covariation of markers occurs only when the
genetic markers are very closely situated in the
gene. Markers that are a few tenths of 1 per
cent apart can show an extensive degree of
covariation in the form of suppression.
Therefore, if we can extend these results, it
is likely that the markers of the first group, the
temperature, the d, the growth requirement, the
MS and neurovirulence, and probably also the
adsorption marker, discussed earlier, belong to
a very small fragment of the genetic material
of the virus.
If so, one would explain covariation as follows:
If we have a protein containing a certain
number of active groups, each one of these
markers could reflect the function of one independent
group. When there is a mutation in
one of these groups, the functionality of the
neighboring group would be affected, as we
know from protein chemistry, and covariation
would be produced.
Thus, lots of covariations we see are not due
to the fact that markers are mixed, i.e., have a
common identical genetical determinant. The
covariation of many characters with neurovirulence
can be explained as follows. These markers
would correspond to functional groups near
the group responsible for neurovirulence. One
would be inclined to predict that there does exist
a special group responsible for neurovirulence.
To proceed in this kind of work, one should
try to find possible markers reflecting the function
of this group, which can be tested in vitro.
From what I have heard this morning, I must
say that the results mentioned by Dr. Hodes, Dr.
Robbins, and Dr. Lépine give the impression
that perhaps their marker has to do more directly
with the neurovirulence than any other
character. Because it is very possible that the
neurovirulence is essentially an expression of a
surface property of the virus, related to the attachment
of the virus to special receptors or
special types of cell, namely, the neurons, or
maybe another cell, which could be from what
Dr. Smorodintsev has just stated, perhaps a cell
involved in allowing viremia.
CHAIRMAN ANDERSON: Are there any comments
on Dr. Dulbecco's statements? Dr. Sabin.
DR. SABIN: I believe that when we have spoken
of correlations of these findings, we have neglected
to mention one property which I described
several years ago, namely, the property of
combining with the neuron receptor substance.
I showed that virulent Type 1 poliovirus combined
readily with suspensions of gray matter
from monkey, chimpanzee, and human spinal
cord, but did not combine with that derived
from rabbit or dog spinal cords. At that time,
I also showed that the Type 1 vaccine strain
combined very poorly with the receptor substance
of monkey, chimpanzee, and human material.
Now the question is whether the specific receptor
substance derived from susceptible nerve
cells possesses physical properties which are the
reverse of the colloids described this morning,
which have greater avidity for the a:tenuated
than the virulent virus.
There is one other point I would like to add
to what Dr. Hodes has presented. When I am
asked for certain viruses, I am given a prescription
and I try to fill that prescription. When I
sent him the two strains of virus excreted by a
child that had been fed Type 1 vaccine, I selected
the one child that showed the maximum
change in the monkey tests observed with Type
1 excreted virus. That maximum change was
observed only after inoculation of 10 million
tissue-culture infective doses intracerebrally.
With smaller doses there was no effect, so we
were still dealing with a highly attenuated virus.
DR. BODIAN: I would like to ask Professor
Smorodintsev whether he has continued to subculture
his fecal isolates in his consecutive human
passages before monkey inoculation, and
whether he feels that the use of tissue-culture
passage fluids instead of fecal suspensions may
influence the picture of reversion of neurovirulence.
DR. SMORODINTSEV (through an interpreter):
I should like to say that, as we have already
published in our works, we have observed a
rather well-defined process of periodical increase
of neurovirulence, particularly with strains of
Type 3; we did not use additional in vitro pas-