#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."

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