[Email Exchange between David Baltimore and Bruce Weniger]

Weniger, Bruce
From: Weniger, Bruce [CORP/NIPI/bgw2]
Sent: 5-Jun-97 18:22
To: Baltimore, David (MIT)
Subject: Subtype E gpl20 is "wild-type"
From: Weniger, Bruce
Date: 5 June, 1997 17:21
To: Baltimore, David (MIT)
Cc:
Subject: Subtype E gpl20 is "wild-type"
Dear David,
I would agree that, in hindsight, it would have been
better for the subtype B gpl20s that began the R&D process
in the 1980s to have used a primary, macrophage-tropic
virus (the kind that is transmitted from person-to-person)
as the seed stock for gpl20. One certainly always wants
to make an effort with ones best shot. Although I think the
desire to hit a home run on one's first step up to the plate
is self-defeating.
You might not know, however, that the subtype E
gpl20 which has begun clinical research in Thailand
was derived from an asymptomatic, recently-infected
Thai. The CM235 strain is not tissue culture adapted, nor
even adaptable at this point. It's parent primary isolate is
macrophage-tropic. I understand the performance
attributes of this protein in small animals and primates are
significantly different from earlier versions of gpl20,
including recognition, binding and neutralization of a
broader array of tissue culture-adapted HIVs.
As you probably know, there is very little neutralizing
activity against primary isolates (including CM235) using the
standard in vitro PBMC neutralization assay. However, this
assay is NOT all that physiological; and thus the predictive
significance of it for in vivo protection against HIV is totally
unclear. The presence of primary isolate neuts using existing
assays would be reassuring, but ought not to be required --
since we have no idea about their predictive significance.
It is certainly your prerogative as the lead AIDS
vaccine advisor to the NIH to make a judgement call that
primary isolate neuts should be required in order to
proceed with a candidate vaccine. NIH could then focus its
efforts on supporting development of candidates that can
induce this response.
Some vaccinologists do not share such unvalidated
assumptions. No mere mortal can honestly say they know,
a priori, that the presence of primary isolate neutralizing
antibodies is predictive of human protection (in fact, there is
in vivo data to the contrary in the chimp-HIV challenge studies).
Nor can one predict with omniscience that the gpl20
approach will fail.
So why are others being impeded in the pursuit of

these scientific hypotheses with their own funds? Such
opposition appears to be a somewhat hubristic attempt at
ideologic censorship.
5571095.0495.072
I suppose the proof of whether ideology is behind
these efforts will come at the time when one must design