Biotechnology's Awe Full Prospect

Marc Lappé, Ph.D.

The discovery almost twenty years ago of how genes could be moved from one organism to another, the bedrock of genetic engineering, has inspired tons of print but remarkably little insight.  “Genetic engineering” has been occurring in nature for eons. It “works” because all organisms have a common genetic core, read a common genetic language, and use the same code for making their proteins, ultimate proof, if any were still needed, of the common origin of all living things.

The universality of the genetic code has permitted thousands of genetic experiments in transforming living organisms.  Indeed, the biggest challenge facing most living things is keeping their own hereditary lineage secure from genetic interlopers.  Nonetheless, genetic contamination from unrelated species occurs at a remarkably high rate in nature. This incursion of novel DNA poses an extra burden to living systems, initially unrelated to their own needs.  Over time, for example, we have incorporated primordial genes from bacteria into our mitochondria.  Thus, gene “contamination” from one organism to another is not only commonplace, but appears to pose little risk of harm.

Ironically, these two feats of nature were what the earliest genetic engineers used to usurp bacteria and plant cells to do their own bidding.  One of the earliest genetic feats was to force a bacterium to make most of the human insulin molecule.  Later, plants were given novel genes which were artificially incorporated into the genetic material of A. tumefaciens, and thereby hitchhiked into the plant cells which this organism infects. Currently, much more sophisticated techniques are used to isolate DNA sequences,  mark them with special flagging genes, insert antibiotic resistance markers, provide them with their accompanying “start” and “stop” instructions, and then literally shoot the whole kit and kaboodle into a target plantlet.  This process of gene insertion is called “biolistics”.  It  is but one of the proliferating technologies in the armamentarium of genetic engineers.  So much for demystifying genetic engineering.

“So what's the big deal?”  From the viewpoint of an industrial genetic engineer, putting a single extra gene sequence into the whole genome of a grain species with some 50,000 or so genes is a drop in a vast DNA pond.  This reality trivializes the potential magnifying effect of even a single new gene in a host genome.  One gene mutation (and there are over 500 to chose from) in the cystic fibrosis gene can cause physiological havoc in a human patient.  Similarly, a single mutation for a tumor suppresser gene in a single cell can release its from growth controlling constraints, and lead to a fatal malignancy.  More to the point, many single genes have dramatically diverse effects, known by the technical word “pleiotropy”.  The gene for muscular dystrophy produces a host of physiological effects.  Similarly, in the mouse, a single gene which permits a vitamin A to produce cell damage can produce a cascade of birth defects in a suitable genetic background.

Hence, it should come as no surprise that many “simple” genetic engineering feats in which a known gene with a known product has been put into a cell has produced a plethora of unexpected and unexplained downstream effects.  We may be witnessing such impacts in transgenic cotton plants which have been reported to have developed deformed roots or “parrot-beak” bolls.  Another example is the genetically engineered variety of fermentation bacterium which was used to make excess amounts of a commercially valuable amino acid supplement called tryptophan. This variant also made several unexpected (and undetected) contaminants, one of which appears responsible for a devastating illness called eosinophilia myalgia.

We might profitably look to human genetic modification for treating genetic disease for guidance.  Human genetic engineering, in which precisely corrected genes are transplanted in cell lines back to a genetically deficient host, has been remarkable for its failure.  Out of over 175 trials, barely a half dozen have proven even modestly effective.  Clearly, we have much to learn about the expression of new genes in a secondary host and how and where they are incorporated into the cells of the body.  These clinical failures have led to the reluctant conclusion that we as yet do not know how to genetically engineer cells in whole organisms and have them work as planned.  The humbling realization has led to a chilling effect on the efforts to go hog-wild to correct gene deficiencies in people through genetic engineering.  This braking has not been because of any lack of genetic enthusiasts to pursue their trade, but largely because of the buffering effects of Human Subjects Committees which have argued for caution and care in human research.

As important as checks and balances of this kind are in science, they have rarely stopped entrepreneurs in the industrial sector.  Virtually no constraints currently temper the rush to application in the area of agricultural biotechnology.  Here, the argument goes, no one can really be hurt by the inevitable “kinks” and “wrinkles” (to use a corporate biotechnologist’s term) which come with early efforts at genetic transformation.  After all, plants are not people. In agricultural biotechnology, unlike human genetic technology, no Research Advisory Committee exists to urge caution or to look to the bigger picture before vouchsafing the very young and very raw technology of transgenic manipulation.  (A short-lived Biotechnology Advisory Committee formed in the late 1980s was disbanded in 1996).  Only the USDA and marginally, the EPA, stood in the way of novel plants being spread by the millions over our waving fields of grain.  And once these agencies bought the argument that genetically transformed plants pose no more risk of gene spread, weediness or ecological damage than do conventional crops, the gate was left open for any and all entrepreneurs to move into the fore. Unfortunately, the number of  “kinks” in the first generation of  transformed plants has been showing up with unexpected frequency.  Early transgenic soybeans (Roundup Ready varieties) failed to live up to their expected yields.  Transgenic cotton crops, first in Mississippi in 1997 and now, perhaps, in Texas for the 1998 growing season, have shown disturbingly high rates of failure possibly attributable to the addition of a new gene.  Even with newer varieties,  it is still arguable that transgenic crops have not kept up with yield expectations. All in all, it looks as if the small farmer is bearing the brunt of the first few years of experimentation.

It would be a great mistake to say the grand substitution of genetically engineered for conventional crops has been an untarnished success, or to discount its failures.  What is really at stake is a vast test of what ethicists call the Opportunity Principle.  This principle says simply, that in some things we really have only one chance to make it right—and that mistakes made in committing to one technology can produce a proliferating set of downside effects. The Opportunity Principle also asks that we look at what is not being done, while thousands and thousands of acres of land are put under the genetic plow.  Instead of conventionally breeding for resistant plants, the artificial insertion of genes for an insect-repelling toxoid converting the entire plant into a toxic brew has led to the acceleration of resistant pests.  This consequence may prematurely doom this natural pest control technology.

Similarly, the assumption that transgenic plants are limited in their ability to pass genetically modified pollen to nearby related species (including weeds) appears wishful thinking.  Research appearing in a September issue of Nature demonstrates that the pollen from transgenic plants can unexpectedly fertilize neighboring related plants and increase their fitness, directly contradicting this expectation.  Unlike the human situation where we have let prudence temper our experimentation and enthusiasm for genetic engineering, we have let crop plant genetic tinkering go on and on at the whimsy of the producers.  To date, as we document in our new book, Against the Grain (Common Courage Press, Monroe, ME), the rationale for engineering choices has had little if anything to do with human needs or the common good.  By selecting only those genes which confer tolerance to their chemical products, many producers appear to be feathering their own nests—at the consumer's expense.

I would like to see some ground rules for genetic engineering in agriculture put into place.  I think gene engineers should be held to the standard not only to prove that their gene “works“ in their targeted plants, but that to know where the gene is, how the gene will perform in the second and third generation of breeding, and to design fail safe crops where the altered gene can be removed or neutralized if necessary.  I think that extensive field testing is essential to demonstrate safety, beyond the simple one to two year trials now run.   And, I believe a National Crop Line Protection Commission should be established to ensure the protection of the germ plasm of our domesticated food crops and the protection of their weedy lineages.

Finally, I think we should all take a collective deep breath, pause and examine closely the apparent failures of cotton and soybean crops which have had their genes tinkered with.  To do less is to do a disservice to the American farmers who have increasingly bought into this technology.  We should not ask them to bet their farms on a fledgling and undeveloped technology.