68 R. Weppelman

April 13, 1986), provides an example of the use of recombinant DNA tech-
nology to attenuate a pathogen. In this particular case, the gene encoding
an enzyme which allows the virus to attack nerve tissue was deleted (Bio-
technology News, April 18, 1986, p. 1). Because the mutation responsible
for attenuation is a deletion, reversion to virulence is virtually impossible.


INTERFERONS AND INTERLEUKINS

 Viral interference, which refers to the relative resistance of a cell al-
ready infected with virus to infection by a second virus, was first noted in
the 1930s (Hoskins, 1935; Findlay and MacCullum, 1937). The term "In-
terferon" was coined two decades later by Isaacs and Lindenmann (1957)
who demonstrated that the resistance was due to soluble factors produced
by infected cells. These factors were subsequently shown to be proteins
and three general types of interferon have been identified in humans: al-
pha, beta and gamma. The three classes are chemically distinct and tend
to be produced by different cell types (Friedman and Vogel, 1983): alpha
interferon by leucocytes; beta interferon by fibroblasts; and gamma inter-
feron by lymphocytes. Genes for all three have been cloned and, while
there appear to be only single genes for beta and gamma interferon, there
are a minimum of 14 genes for alpha interferon which vary 15 to 30 per-
cent in amino acid sequence (Friedman and Vogel, 1983; Derynck, 1983).
Whether these are alleles or "pseudogenes" (i.e., DNA sequences which
are not expressed) is not clear.
 The biological actions of the interferons are broadly similar. In addition
to being antiviral, they inhibit replication of both normal and tumor cells
(Brouty-Boy6, 1980). All three classes modulate the immune response in
ways which are difficult to predict (Levy and Riley, 1983; Epstein and
Epstein, 1983; DeMaeyer-Guignard and DeMaeyer, 1985). Whether the
response is augmented or attenuated depends on the antigen, the immune
response measured, and the treatment schedule (i.e., was interferon given
before, after, or at the same time as antigen).
 In view of the wide range of activities, it is not surprising that the inter-
ferons have rather serious side effects. According to Scott (1983), "It has
become apparent that interferon itself is not innocuous; indeed it was
never reasonable to consider that it would be." All interferons appear to be
pyrogenic and induce in humans a collection of side effects which can best
be described as "flu" (Scott, 1983). Growing children congenitally infected
with virus stopped gaining weight when treated with alpha interferon and