The Genius of Louis Pasteur

and provides a fundamental insight into one mechanism
that brings about the profound suppression of the immune
system seen in patients with AIDS, acquired immune deficiency
syndrome.
The significance of this breakthrough is not simply that it
could prevent vaccinated individuals from becoming infected.
More important, it could also prevent those who
are carrying the virus, but have not yet developed active
disease (the asymptomatic carriers), from developing AIDS
or one of the other deadly conditions associated with the
AIDS virus. These people, once identified in a mass-screening
program, could be treated with such a vaccine, thereby
preventing them both from developing AIDS and from remaining
a carrier of the disease. In other words, this breakthrough
makes it possible to stop the spread of AIDS; what
is required is a mass-screening to identify infected individuals,
combined with a full-scale national mobilization to
rapidly exploit the promise of this breakthrough.
Although the possibility of a vaccine against the AIDS
killer is a dramatic breakthrough, the importance of this
new technology in also providing the capability to quickly
develop a screening test for the presence of the AIDS virus
should not be underestimated. The present tests used cannot
discern the presence of the virus itself; they test for
antibodies to the virus. A test for the virus itself would
eliminate the vexing problem of the antibody negative virus
carrier, as well as certain risks involved in growing large
quantities of AIDS virus for preparation of the current test
kits. Since the antithymosin antibody reacts with a highly
conserved region of the virus (one that does not mutate
easily), there is almost no problem with failure to detect
mutant strains of virus.
The Thymus Clue
Most previous attempts at producing a vaccine for the
AIDS virus have concentrated on the external envelope of
the virus, on the assumption that this part of the virus would
be most accessible to attack by a vaccine (Figure 1). AIDS is
a retrovirus, a group of viruses formed by the action of RNA
on DNA instead of the usual, reverse process. Unfortunately,
the particular part of the AIDS retrovirus genome,
the envgeneiFigure 2), that codes for the external envelope
is highly mutable, and a vaccine produced against one form
of the virus may be totally ineffective against another form
of the same virus, varying only in the envelope. Also, most
antibodies produced against the envelope do not appear to
be neutralizing antibodies.
The antibodies produced in response to thymosin a-1,
however, react with a protein that is coded for by the gag
gene, whose products form the internal protein capsid surrounding
the genetic material of the virus. These genes are
highly conserved in retroviruses and do not display the
genetic drift characteristic of the env genes. As a result, a
vaccine prepared against this protein, known as p17, could
be expected to be effective not only against the various
AIDS viruses, but also against related retroviruses.
This breakthrough was the product of research by Dr.
Allan L. Goldstein of the George Washington University
School of Medicine in Washington, D.C. Goldstein had
been struck by the clinical similarities between AIDS patients
and children with rare primary immunodeficiency
Figure 1
DIAGRAM OF A TYPICAL RETROVIRUS
The AIDS virus is one example of a retrovirus, a term
that refers to a group of microorganisms formed by
RNA acting on DNA, instead of the usual, reverse
process. The retrovirus core consists of the RNA genome
of the virus, along with the enzymes for converting
the viral RNA to DNA within the cell (the "reverse
transcriptase"). Surrounding this are the internal proteins,
p24andp17. Antithymosin a-1 antibodies crossreact
with p!7 and apparently interfere with assembly
of the virus. The internal proteins are in turn surrounded
by an envelope derived from the membranes of
the host cell. Most attempts to produce a vaccine have
centered on trying to produce antibodies to the envelope.
Source: "Retrovirus Vectors for Gene Transfer: Efficient Integration into and
Expression of Exogenes DNA in Vertebrate Cell Genomes." to be published in
Gene Transfer, ed. R. Kucherlapati {New York: Plenum Press).
Figure 2
ARRANGEMENT OF GENES IN A RETROVIRUS
The arrangement of genes in the RNA of a retrovirus
is shown in (a). The term pbs refers to the primer
binding site, where the enzyme for copying the RNA
to DNA binds to the RNA to start copying. The term
gag is the gene coding for the internal proteins shown
in Figure 7, while pol codes for the enzyme that converts
virus RNA to DNA within the cell. The gene coding
for the envelope is called env.
The same sequence translated into DNA and inserted
into the genetic material of the host cell is shown
in (b). LTR stands for long terminal repeat, repeated
sequences of genetic material that are characteristic
for insertedproviral DNA.
Source: "Retrovirus Vectors tor Gene Transfer: Efficient Integration into and
Expression of Exogenes DNA in Vertebrate Cell Genomes." to be published in
Gene Transfer, ed. R. Kucherlapati (New York: Plenum Press).
FUSION September-October 1986 41