|
|
#2
from R&D Innovator Volume 1, Number 1
August 1992
On
the Virtues of Tedium
by
Paul Christou, Ph.D.
Dr.
Christou is Senior Scientist, Agracetus Inc.
I
should have foreseen some excitement when I began collaborating
with a scientist whose hobby is fireworks, but I never expected
that we'd invent a new "gun" that--with electricity
instead of chemical energy-- would greatly simplify the production
of genetically engineered plants.
Ever since the Turkish invasion of my homeland, Cyprus, I've
learned to question opinions that many people accept as axioms.
That's because the invaders shattered all my dreams,
threatened my life, and killed my friends before my eyes.
Because
my colleague Dennis McCabe and I were both working outside our
expertise (he's a mycologist, I'm a chemist), we brought no
conventional wisdom to our genetic engineering project.
And that, I feel, was critical to our success.
But
there was another factor, one that seldom appears in the
scientific literature. That
factor was frustration at the tedious task of producing
genetically engineered plants with tissue culture.
It's a rigorous process that requires phenomenal
observational skills and repeated manipulation of miniscule plant
tissues. Tissue
culture requires entire days spent at a noisy sterile hood, facing
a stainless steel wall. (Sterility
is vital because a microbial contaminant can torpedo an entire
year's effort.)
Unless
you think a scientist's mindset influences research, none of this
is relevant to genetic engineering.
But as this history will demonstrate, frustration and a
healthy disregard for conventional wisdom can quite be useful to a
scientist.
When
I was hired in 1982, I didn't expect to be working with guns, or
with genetic engineering either for that matter.
While growing up on Cyprus, I'd been fascinated by science.
But I also watched vicious battles between the Greeks and
Turks. I joined the military academy and learned the value of
taking risks and continually searching for better solutions.
I moved to England to complete undergraduate, doctorate and
postdoctoral work. I
concentrated on biosynthesizing complex organic molecules in plant
tissues. Because
Agracetus was interested in this area, I was hired to begin a
program for using plant cells to produce valuable chemicals.
Unfortunately, by the time my U.S. visa was granted, the
company had dropped that program and was focusing on genetic
engineering of important agricultural plants.
When I finally arrived, I was assigned to an analytical
chemistry problem unrelated to genetic engineering.
At
that time only tobacco was amenable to genetic engineering, and
just about everyone in the field was introducing genes into single
or clumped tobacco cells. After
the foreign genes had joined with tobacco's chromosome, the
scientists used tissue culture to regenerate the cells into mature
plants. With luck,
and a great deal of work, the seeds of those mature plants would
contain the foreign gene. Sometimes, more than a year was needed
to analyze the results.
Because
the work was obviously quite tedious, I felt fortunate to be
working on anything else. But
that liberated feeling vanished when the company decided to focus
on its primary project—engineering agricultural crops.
Even though I had no experience with molecular biology or
plant regeneration, I took my turn at the hood, trying to see
which (if any) media would induce the cells to grow into
seed-bearing plants.
I
was not impressed as I joined dozens of able scientists gently
coaxing plantlets from a soup of cells.
I kept thinking that if regeneration through tissue culture
were essential for genetically engineering plants, then anybody
working toward that goal faced a lifelong sentence of tedium.
Because
I wanted to find a better way, I was receptive when Dennis
mentioned some unusual weaponry--an electric "gun" he'd
built on the sly. I responded, "Anything to get out of tissue
culture!" and sneaked in some extra time to work with him. Using an electric discharge, the machine propelled
microscopic particles of gold which were coated with DNA at living
cells. We tried the
method on soybean cells and found that the new genes did function
in the offspring. That
was half the battle.
But
we still had to tissue culture the altered cells to get engineered
plants. I'd read that
soybeans could be regenerated from a tiny region inside the seed
called the meristem--the actual "germ" of the seed.
Although other genetic-engineering techniques could not
introduce genes into the meristem, we tried Dennis' machine, and
soon found that it could insert genes in the meristem without
killing it. Just as
important, these meristems developed directly into mature plants,
and that bypassed the laborious manipulations of tissue culture.
Many
Agracetus scientists initially seemed rather blase about our
results--perhaps they simply didn't believe them.
But when we successfully repeated the experiment, they
abandoned tissue culture and began using the electric particle
accelerator with all of Agracetus' target crops.
As
outsiders to the field of plant genetic engineering, we weren't
afraid to go ahead, even though experts told us we were wasting
our time. I should
stress that the initial experiments were done on our own
time--Dennis and I were both working full time on other company
assignments, and we started the crucial test at 4 a.m.
Shoot-em-up
Using
our "gun," Agracetus became the first company to
genetically engineer important commercial lines of soybean,
cotton, corn, bean and rice.
In fact, we now sell a genetic engineering service using
this device to companies that far out-spent Agracetus in trying to
introduce genes into crops.
It's
ironic that our competitors depend on us for a key part of their
work. Looking to the
future, I can see another irony.
Although we are continually improving the gun, I won't be
surprised if somebody else invents a better process, one that
eventually overtakes ours.
After
all, now we are the "experts."
|