Andrew Maykuth Online
The Philadelphia Inquirer
January 10, 1986
Genetic wonders to come: Some see boon, others calamity

If all goes as planned, scientists within about a month will venture into a California strawberry patch the size of a typical suburban lot and spray the young plants with about eight trillion bacteria.

The bacterium, Pseudomonas syringae, is nothing out of the ordinary - it is one of the thousands of microorganisms that live innocuously in the soil, air and water of this planet, peacefully coexisting with humans and other forms of life.

But in this instance, it represents a biotechnical revolution. With one gene removed by scientists, it will be the first genetically engineered organism to be released into the environment.

In its natural state, the microbe attracts ice crystals, causing frost to form on plants. This version, however, is designed to inhibit freezing, thus protecting the strawberries from an early, killing frost.

Agroeconomists believe that this strain of the bacterium - called "ice minus" - could reduce the billions of dollars' worth of crops lost each year to frost. Its commercial use could extend the growing season in colder regions by up to two weeks.

And compared with other genetically altered organisms on the drawing boards, ice-minus is a mere cave drawing.

For the coming decades, researchers are forecasting a host of genetically designed wonders - plants that require little fertilizer because they can draw their nitrogen from the air, microbes that consume oil spills or detoxify hazardous waste, crops custom-designed to kill insects and vaccines for dreaded diseases.

Even yesterday's announcement of the development of a nasal spray that appears to help prevent the common cold came as a result of gene research: Interferon, the once-rare antiviral substance used in the spray, can now be mass-produced, thanks to gene-splicing.

A growing number of environmental groups, however, are seeking to dampen the enthusiasm impelling the new technology. They are particularly cautious about introducing new organisms into the environment, where they could reproduce with unforeseen consequences.

For instance, some scientists believe that the same chemical structure in the bacterium that causes ice crystals to form on plants also causes ice crystals to form in the atmosphere, an essential step in the formation of rain clouds. Should ice-minus reproduce and dominate its parent bacteria in the environment, skeptics warn, it could reduce rainfall, or worse, cause a drought.

"These are weird problems," said Jeremy Rifkin, president of the Foundation for Economic Trends in Washington, which in November sued the Environmental Protection Agency (EPA) to stop the strawberry-patch experiment until it assesses the risks. He believes that the issues will be magnified as researchers seek approval to release other new microorganisms into the environment, with unpredictable results.

Research firms argue that too much regulation will hinder a growth industry that is just a decade old, creating a competitive advantage for Japanese and European researchers.

"There are some people who think if something is genetically engineered, it's frightful," said Harvey S. Price, executive director of the 48-member Industrial Biotechnology Association. He said the purpose of the California experiment was to address the concerns that critics have raised.

"Noboby's talking about killer tomatoes or the Andromeda Strain," said Rifkin. "We're talking about more subtle things, about the relationships of these things in the environment."

Skeptics believe that only a few of the genetically altered microbes will cause environmental problems, but that the problems could be calamitous.

"If history has taught us anything, it is that we have a litany of problems with pesticides and leaks of toxins . . . and other things that were introduced into the environment," said Jack Doyle, director of the Agricultural Resources Project of the Environmental Policy Institute in Washington.

"If we reflect on our recent technological problems, it should give us pause."

*

The products of biotechnology are already being commercially produced, locally and around the world, and some will soon be found in supermarkets and hospitals.

Medical firms such as Centocor Inc. of Malvern have been producing such products as human blood serum and monoclonal antibodies, the microscopic "guided missiles" that can be designed to seek out specific disease cells.

DNA Plant Technology Corp. in Cinnaminson this year will test-market extra tasty carrots and celery it devised through a "tissue culture" technique that is an accelerated form of traditional plant breeding.

Charles Van Horn, the head of the biotechnology section of the U.S. Patent Office, said his staff had tripled in the last two years, from 13 people to 38. Nevertheless, they are falling behind in reviewing patent applications.

"You could say there has been a real increase of activity," he said. This year, according to rough industry estimates, $700 million will be devoted to research and development of biotechnology, a slight increase over last year.

Much of the technology involves the manipulation of DNA (deoxyribonucleic acid), the chemical that is present in every living cell and that makes up the genes that determine each characteristic of that organism. DNA is the genetic blueprint.

By manipulating DNA, researchers can clone an organism many times over, each time creating an exact duplicate. Medical firms such as Centocor, for instance, have cloned antibodies that are now used for diagnosing and treating specific disease cells. Centocor's cancer-testing kits, for instance, are now sold abroad. The most difficult part of the process, the company says, is identifying the antibodies, which occur naturally in humans.

Likewise, researchers at DNA Plant Technology cross-breed plants by mixing their cells in petri dishes, hoping that one cell will adopt the desirable genetic characteristics of the other. When they achieve a marketable combination - a particularly sweet carrot or celery without stringy fibers - the scientists can reproduce the cells through cloning.

"It allows us to do what breeders have done for years, perhaps more quickly and perhaps more selectively," said Dick Laster, president of DNA Plant Technology.

Those techniques rely more on chance to achieve a desired genetic combination than the gene-splicing involved with ice-minus, where a researcher actually identified and removed a specific gene that was controlling the bacterium's ice-formation properties. The technique is also referred to as "recombinant DNA."

The discovery of the way in which ice crystals form on plants was made by Steven E. Lindow, a plant pathologist at the University of California at Berkeley. The crystals form around an enzyme secreted by Pseudomonas syringae, which is present on most leaves. By removing the gene that controlled the creation of the enzyme, Lindow found that plants coated with ice-minus could survive in temperatures as low as 23 degrees Fahrenheit. Untreated plants froze and died at 32 degrees.

Lindow sold the idea to Advanced Genetic Systems Inc. (AGS) of Oakland, Calif. Two years ago, AGS applied to the federal government for a permit to test ice-minus.

Rifkin's group at that time sued the government, contending that it had no clear mechanism for handling biotechnology applications. As a result of that lawsuit, the government put the ice-minus application on hold. A year ago, the White House shifted responsibility for the applications from the National Institutes of Health. Now, the EPA approves genetically engineered pesticides, the Food and Drug Administration handles gene-spliced drugs, and the Department of Agriculture reviews new plants.

In November, the EPA approved AGS's strawberry-patch experiment, which the agency plans to monitor. "We decided the risk was sufficiently low that they go ahead with the field tests," said William Schneider, the EPA microbiologist who reviewed the ice-minus proposal. "We conducted a reasonable, complete and thorough examination."

The EPA's Hazard Evaluation Division, in reviewing the application, concluded that ice-minus would probably migrate outside the strawberry patch and could survive indefinitely. However, the researchers contended that because ice-minus is "genetically deficient," in that its ice-making gene has been removed, it would not dominate its parent bacterium in the environment.

Environmentalists, though, say U.S. history is replete with examples of non-native creatures' proliferating disastrously after being introduced into an environment for a specific purpose; gypsy moths, starlings and kudzu vines are among those cited.

"You put a microbe out there," said Rifkin, "you can't recall it and put it in a steel drum." His lawsuit is still pending and could affect the planned ice-minus release.

Besides the possible reduction in rainfall, skeptics worry that ice-minus could inadvertently prolong the growing seasons of many plants, possibly disrupting a delicate natural balance in the food cycle.

*

The controversy developing over the ice-minus experiment only foreshadows the clashes possible when more research firms try to introduce more complicated organisms.

The only other application pending before the EPA for a gene-spliced creation involves a proposal by the Monsanto Chemical Co. to incorporate a naturally occurring insecticide into a soil bacterium, which would be used to coat corn seed. The proposal is more advanced than ice-minus in that it involves incorporating the insecticidal gene into the bacterium, rather than merely removing a single gene from a microscopic organism.

The potential for such an insecticide would be immense: Theoretically, the new organism would thrive in the soil along with the corn plant, protecting its roots from black cutworms. With reduction of infestation, production would increase.

Other research that reportedly is in the works would go one step further than the Monsanto application by amalgamating the insecticide with the plant itself, rather than within a soil bacterium. Scores of research firms are trying to devise such insect-killing plants, including a team at Temple University headed by biologist William R. Harvey.

"You remember the space program, when all those rockets were blowing up on the launching pad?" said Harvey. "Well, the science (of gene-splicing) is at that stage now."

Harvey's team is studying Bacillus thuringiensis, a naturally occurring bacterial insecticide commonly known as BT. Most of the research into genetically designed insecticides involve various forms of BT, some of which affect specific insects. The Monsanto application involves a type of BT that is believed to kill only black cutworms.

The Temple researchers are trying to identify the BT genes that produce the insecticides in order to fuse those genes to plants. "All we're doing is what nature is doing all the time," said Harvey. "We're just doing it in a directed way."

Harvey's research budget is $227,000 this year, with the bulk of it coming from the National Institutes of Health.

Howard T. Dulmage, a U.S. Department of Agriculture scientist in Brownsville, Tex., who has isolated several BT strains, said he had doubts that regulators would treat the insect-resistant plants as merely a slight aberration from nature.

"I question whether this will be approved by the regulatory agencies, because you're introducing a toxin into a plant," he said. "I don't think anybody knows what the long-term effect of that will be."

Officials of Rohm & Haas Co., which is contributing $30,000 to Harvey's effort, announced earlier this year that a European research team it is sponsoring had spliced BT genes to the cells of a plant. But they declined to disclose whether the plant effectively killed insects, noting that their competitors were involved in similar research.

"Because of the competition and the dollars at stake, these companies are playing this so close to the vest that we only learn of their plans when they apply for a permit," said Doyle of the Environmental Policy Institute.

The EPA's Schneider acknowledged that the new microorganisms would present a difficult challenge to regulators, but not an insurmountable one. "You know an organism will kill one target species, but you're not sure what else it will affect," he said. "So you test it against a representative cross section of other species. It's the same with chemicals."

But Doyle argues that the microorganisms are living creatures, not toxic chemicals. "The microbial realm is different from petrochemicals," he said. "We're in uncharted territory there. We don't know a hell of a lot about unaltered organisms and why they occupy a particular niche in the ecosystem.

"We're on a breakthrough of a really fundamental knowledge in the plant sciences. Some of these applications may be very productive and have the net beneficial effect in the long run of reducing our reliance on pesticides."

The naysayers acknowledge that the technology, powered by a potent commercial and political momentum, will prevail over their calls for caution. Said Rifkin: "It's part of our cultural tradition - 'If it can be done, do it. Let's worry about the consequences later.'

"There may be a lot of benefits to this technology, but there's a lot of costs. . . . If we don't discuss these questions at the beginning of the technological revolution, then the middle of the process will be too late and by the end of the process, it won't matter."


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