April 10, 2000 / Business Week / Catherine Arnst
Tobacco's public image couldn't, according to this story, be more stained
these days, given the war on cigarettes in the courts, federal and state
governments, the medical establishment -- even in Doonesbury. But the
tobacco plant is not an irredeemable ne'er-do-well. Because its genetic
makeup is fairly straightforward and well understood, scientists believe
tobacco could turn out to be the perfect biotech factory for protein-based
drugs.
The story says that by splicing human genes -- a technique developed in the
early 1990s -- researchers have enabled tobacco plants to produce a number
of drugs and vaccines and even human blood components. Within 10 years,
researchers are hopeful that tobacco farmers might be raising millions of
acres of biofactories rather than "the killer weed."
The latest breakthrough in tobacco "pharming" may bring such a vision one
step closer to reality. Scientists at Monsanto Co. were cited as reporting
in the March issue of Nature Biotechnology that they were able to
genetically engineer tobacco plants to produce human growth hormone,
otherwise known as somatotropin -- an extremely costly drug used to treat
dwarfism. But the Monsanto discovery was more important for the process than
the product. The scientists were able to induce the tobacco plants to
manufacture the drug in an abundant piece of the plant cell known as a
chloroplast, which is responsible for converting light into food. Other
efforts to create drug-producing plants have altered plant nuclei instead --
far less numerous cell components.
Jeffrey M. Staub, manager of the Monsanto team that developed the
technique, was quoted as saying, "We were able to produce 300-fold more
human somatotropin in the chloroplasts than in the nucleus. As an optimistic
scientist, I think it is very reasonable to [believe] we will be able to
produce commercial quantities of human proteins in the plants in the next
couple of years."
The biotech industry has been seeking an inexpensive way to produce its
products almost as strenuously as it has been searching for the treatments.
Old-fashioned drugs are essentially chemicals that can be cooked up in
factories, but bioengineered treatments are usually large proteins, and they
need to be "grown" -- typically in bacteria. Only very small amounts of a
drug at a time can be produced this way, and only in a tightly controlled
environment.
Some biotech drugs are also secreted in the milk of genetically engineered
animals, but raising farm animals is expensive and time-consuming, and
separating the drugs from the viruses and bacteria in the milk can be
difficult. Plants, however, are both cheap to raise and carry virtually no
risk of contaminating the drugs they are used to create -- making them the
ideal bioreactor.
The story goes on to say that even with plants, though, volume remains a
problem. All plant cells contain subunits called organelles, two of which
are the nucleus and the chloroplast. Gene splicing to date has focused on
altering the nucleus -- essentially the brain of the cell, because it
controls all of the plant's activities. But drug production was limited,
since there is only one nucleus per cell. Moreover, the genetic alteration
is transmitted to the plant's pollen, making it difficult to control the
spread of the reengineered plants. Chloroplasts, however, are abundant, and
they do not spread their genetic changes to any other cells in the plant.
The Monsanto researchers caution that their work is in the very early stages
and was done on a very small scale.
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