AN OVERVIEW OF BIOTECHNOLOGY


 Some general remarks about recombinant DNA technology follow.
First, once a protein or its gene has been isolated, techniques are broadly
available for expressing the gene. The early dependence on E. coli has
vanished. Individual companies have available as many as ten expression
systems, including bacteria, yeast, molds, and mammalian tissue. A year
ago, a postdoctoral student told me, "Anybody can clone a gene." His
statement reflected the situation in some developed countries, but not in
most countries. An important bottleneck is availability of restriction en-
zymes and other substances including tagged biochemicals. Another state-
ment made to me was, "Genentech has cloned every gene that manage-
ment thinks might be of possible interest." That is not to say that
everything has been done, or even most of it. Rather, the statement is made
to indicate that as opportunities and needs arise, the necessary technology
will be quickly applied, provided a financial or other incentive is present.


PROTEIN ENGINEERING

 For several years, the possibilities of changing the content of a gene have
been widely recognized. Progress has been made in this, some of which has
been reported in the literature (Villafranca et al., 1983). The procedure
thus far has been to modify a gene slightly so that when the gene is ex-
pressed, one of the amino acids has been replaced by another. Experiments
have shown that resultant enzyme activity may be enhanced, unchanged,
or decreased. Coincident with this, the folding of the protein and its shape
may be changed. Substantial progress is being achieved in understanding
the mechanisms, and top-notch crystallographers and extensive computer
calculations are involved. Already practical applications are emerging,
and many more can be expected. In its 1985 annual report, Cetus discloses
production of what it calls muteins of natural proteins. Cetus has found
that both the biological activity of the protein and the ease of production
can be enhanced by changing some of the amino acids. In particular, an
improved interleukin-2 was achieved by this procedure. Obviously, a new
chemical form is patentable, and this could be an additional crucial ad-
vantage. In the annual report of Genencor, genetic engineering of subtili-
sin is mentioned. This protein, which is a protease, has been engineered
and expressed in as many as 80 variants. An amino acid at one point in the
molecule has been replaced by all of the other 19 amino acids. Genencor
has been exploring the properties of subtilisin with a view to using it as a
protease in detergents. They have found that by replacing amino acids in