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April 19, 1999
Plant Sterility Research Inflames Debate on Biotechnology's Role in Farming
From NYT
http://www.nytimes.com/library/national/science/041999sci-agri-biotech.html

By BARNABY J. FEDER
 LUBBOCK, Texas -- Seven years ago, Melvin Oliver had one of those middle-of-
the-night "aha!" inspirations that normally occur only in researchers'
fantasies and campy movies. Suddenly, he could visualize how to grow generation
after generation of plants and then, whenever he desired, insure that the next
generation would be the last -- because all its seed would be sterile.

Oliver, a 48-year-old government scientist at the Department of Agriculture's
research station here whose main focus is drought resistance, never dreamed he
would change the course of the increasingly bitter debate over biotechnology's
role in the food chain.
That is what has happened, though, since a joint patent covering his
inspiration was issued just over a year ago to the federal government and Delta
and Pine Land Co., a cotton seed producer that co-sponsored the research. They
saw it as a potentially useful tool for preventing farmers from growing
valuable genetically engineered crops without paying annually for the seed.
Critics, led by Hope Shand, director of research for the Rural Advancement
Foundation International, a farm advocacy organization in Canada, saw it as a
threat to farmers' security, especially in developing nations, and i
mmediately dubbed it "Terminator" after the robotic killer of movie fame. The
 protests have ranged from angry letters to torched research crops. The fact
 that Oliver and his research team have yet to prove the concept wor
ks in field crops has become an almost irrelevant footnote.
"Seed sterility has become a surrogate for the entire debate on biotech," said
 Philip S. Angell, a spokesman for Monsanto Co., the pioneering agricultural
 biotech giant.
Angell said that Monsanto, which has a pending agreement to buy Delta, has
 become so alarmed by the anti-biotech feelings stirred by the sterility
 technology that it wants a thorough, clearly independent international rev
iew of the costs and benefits of the technology and related inventions.
Monsanto wants the review open to a wide range of public interest groups and is
 preparing a pledge not to try to commercialize any such technology until such a
 review is completed and the company has responded to all the
concerns raised, Angell said.
Critics say seed sterility is a particular threat to farmers in the developing
 world, where nearly all subsistence farmers are too poor to buy new seed and
 thus dependent on saving seed or trading with neighbors. Those un
lucky enough to live near a farmer using the new technology could have part of
 their crop sterilized by drifting pollen and never know it until the next
 year's planting, they add.
Because the new technology is switched on by spraying with chemicals just before
 the seed is planted, biotech critics also warn that it is confirmation of their
 charges that multinational chemical companies, which have be
en buying up seed companies, are moving rapidly toward dominance over
 agriculture.
As things stand now, farmers buy new seed for hybrid crops, especially corn,
 each year because the next generation of such plants does not resemble the
 parent. But for most self-pollinating plants, including soy beans, ri
ce, wheat and cotton, farmers can save seeds to replant confident that the
 offspring will resemble the parent. In the developed world, especially in the
 United States, farmers often buy seed each year as well to take adva
ntage of the latest genetic improvements and to avoid the cost of cleaning and
 storage.
Seed companies say the higher profits they might gain from engineering sterility
 would spur even more investment in improved crops. Sterile seed could also
 reduce fears that new traits engineered into crops, like the abil
ity to tolerate herbicides, might jump to weeds. In theory, the jumping traits
 would also carry the genetic instructions to prevent the weeds from
 reproducing.
"We are recognizing now though that there is something psychologically offensive
 about sterile seed in every culture," Angell said.
Biotech critics had not thought much about seed sterility until Delta and the
 Agriculture Department announced their patent. Delta's acquisition by Monsanto,
 a deal held up by a Justice Department antitrust review, fueled
 their alarm because Monsanto, the St. Louis agrichemicals and drugmaker, has
 been by far the most successful company in genetically engineering new crops.
 The critics were even more concerned when they discovered that a
number of large agribusinesses -- including Monsanto -- had already obtained
 patents for sterility processes other than Oliver's.
Finally, several months after the patent became public, critics began to see
 that all the sterility work relied on a powerful new wave of biotech research
 that had gone largely unnoticed: the use of chemicals as switches
to turn specific genes in plants on or off at a particular time. The new
 engineering, they concluded, would inevitably make farmers ever more reliant on
 chemical companies.
Many of the potential applications are more alluring for farmers than seed
 sterility. Some researchers see gene controls as a way farmers could raise the
 level of a nutrient in a growing crop -- say, a specific oil -- if
that output becomes more valuable after the crop has been planted.
Others see the new technology being used to control exactly when a plant
 generates defenses against insects or viruses. They envision, for example,
 spraying an innocuous chemical that would signal engineered genes to quic
kly activate a crop's normal defenses at the first sign of fungal invasion,
 reducing reliance on the harsh pesticides normally used to stop the disease.
Similarly, instead of engineering plants to produce a toxin that kills specific
 insects throughout the crop's growth cycle as the already widely used
 genetically modified corn and cotton do, the new technology could keep
plants from making the toxin unless the crop actually was threatened with
 serious damage. Less exposure should make it much harder for insects to adapt.
"This is the next big breakthrough after discovering how to move genes into
 plants," said Roger N. Beachy, director of the Donald Danforth Plant Science
 Center in St. Louis. "You're talking about exquisite control of how
plants respond."
Beachy and other biotech backers say the new wave of biotechnology is vital to
 feeding the growing world population and preserving the environment. It may
 actually reduce reliance on the most dangerous agrichemicals. If f
armers do not see it as beneficial, they will not use it, they say.
Critics say the problem is that market forces make it inevitable that a handful
 of large businesses will use such breakthroughs in ways that maximize their
 profits, leaving farmers totally dependent on chemicals they manu
facture. With more and more farmers planting fewer varieties of high-performance
 crops, the risks increase that disease or insect infestations could severely
 damage food production and suddenly produce widespread crop fai
lure, they argue.
"It's not the technology itself, it's who will control it and benefit from it
 that matters," said Ms. Shand, of the Rural Advancement Foundation.
The global protest campaign has already led to incidents in which experimental
 plots of the kind of genetically engineered crops Monsanto has sold widely in
 the United States were burned in India under the mistaken belief
 they contained the new sterile seed technology. A number of companies with
 patents that cover sterility applications have rushed to say that they have no
 intention of developing and marketing such crops.
In December, the Consultative Group for International Agricultural Research, a
 Washington consortium of research and international development bodies, voted
 to oppose any use of the sterility technology in the developing
world. The Department of Agriculture attracted withering criticism and thousands
 of angry letters for its role as a co-sponsor with Delta of the research led by
 Oliver.
"The public won't pay for a USDA that is just a farm team for industry," said
 Margaret Mellon, a biotechnology expert at the Union of Concerned Scientists in
 Washington.
Agriculture officials say the criticism has led it to revise its review policy
 on research financing to allow more input from biotechnology critics. But they
 are also anxious that leading-edge biotechnology work not be le
ft solely to the private sector, not least because that makes it harder for
 policymakers to anticipate where agriculture may be headed.
Others, like Geoffrey Hawtin, director general of the International Plant
 Genetics Resources Institute in Rome, add that work with the private sector may
 be necessary because multinationals control crucial patents. Geneti
c engineering, they say, may be the only hope for rapidly improving crops, like
 bananas, that are vital to subsistence farmers and are being ravaged by
 disease.
"It's a technology that can be used safely," said Gary Toenniessen, deputy
 director for agricultural sciences at the Rockefeller Foundation. "If the
 targets are right it could benefit poor as well as rich farmers."
The policy debate has raced ahead of the science. Oliver's team is hoping
 results due this week from tissue samples taken from a batch of tobacco plants
 will finally confirm that their theory works in a real plant. Tobacc
o is widely used in research because it is easy to manipulate genetically, but a
 success with it does not guarantee that the same methods would work on
 important food and fiber crops. Each crop could require its own speci
fic cocktail of genetic changes.
Still, biotech critics and supporters alike are convinced that "chemical gene
 switch" projects will abound -- and some succeed -- even if Oliver's sterility
 project runs into a dead end.
The novelty is not in the genetic engineering techniques -- Oliver, for
 instance, uses standard methods to get foreign genes into plant tissue cultures
 and, eventually, to grow whole plants from them. But chemical switch
systems involve uniquely complicated relationships among the genes being
 inserted.
Oliver's first building block is a gene and control system, or promoter, that is
 capable of generating a toxin that cripples the seed's germination apparatus
 but leaves the seed and the rest of the plant normal in every o
ther respect.
As a safeguard, however, the gene cannot make this toxin until an enzyme breaks
 down a DNA wall the research team puts between the toxin code and the promoter.
 As a further safeguard, this enzyme comes from a second forei
gn gene that Oliver has inserted. Finally, there is a third inserted gene that
 serves as the on-off switch for the whole system.
The third gene makes proteins that block production of the second gene's enzyme.
 But those so-called repressor proteins are designed to have an affinity for a
 specific chemical, in this case the antibiotic tetracycline. W
hen Oliver -- or whoever produces the seeds -- sprays them, the proteins bind to
 the tetracycline instead of the enzyme production sites. When these seeds are
 planted, unlike their unsprayed predecessors, the DNA-cutting
enzymes are made and the gene that makes the sterilizing toxins is primed to
 kick in months later when the plant matures.
"It's quite an elegant solution," said David Culley, a molecular biologist at
 Washington State University.
Oliver figures it could have been done much better -- and done more quickly --
 if he and his colleagues had the kind of budget and access to crucial patents
 available to many corporate biotech researchers.
"If Monsanto had done this, they would be in the field by now," he said.
 Perhaps. But even though researchers have been looking at a wide variety of
 chemical-gene switch combinations, industry sources say no one is close
to field tests on switches in crops for anything other than internal breeding
 programs.
"There is always something wrong," said Stephen Evola, co-president of the
 biotech research arm of Novartis, the Swiss agribusiness and pharmaceutical
 company, noting that the chemical switch had to be safe and inexpensiv
e and its interaction with the plant very specific. Achieving reliable control
 is especially challenging because the behavior of gene promoters, which control
 the timing, level and location of gene activity, is far from b
eing fully understood.
"We are at the very beginning of a long learning curve," said David Lawrence, a
 scientist at Zeneca Group PLC of Britain.
Some chemicals that are extremely useful in the current research phase, like
 steroids, are seen as obvious nonstarters for commercial applications because
 they have strong impacts on animals. Systems based on lactose solu
tions, which are already used as switches for turning on genetic activity in
bacteria, have also been tested in plants. So have copper and ethanol.
Companies are also exploring gene switches tailored to chemicals farmers use
anyway, like fertilizer. Other researchers are studying nonchemical switches
like light, moisture and viruses. They suspect though that plants encounter
such things so frequently and in so many ways that it may be impossible to use
them outside of a carefully controlled laboratory.
Oliver, for his part, is fatalistic about where his contribution will end up.
His office is, with impish defiance, decorated by a large poster of Arnold
Schwarzenegger, the original Terminator. But he repeatedly describes seed
sterility as an underfinanced diversion from his studies of drought-resistant
moss.
"I'm very confident the science will pan out," he said. "But this technology
will flourish or die for reasons I have no control over."

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