Who Will Regulate It, and How? : Genetic Engineering Has U.S. Officials in Quandary
Three years ago, Steven Lindow was an inconspicuous scientist at the University of California whose research project--finding a way to reduce frost damage to crops--did not rate the media attention accorded to more glamorous undertakings.
Today, however, Lindow is a nationally recognized spokesman touting the potential benefits of applying genetic engineering techniques to agriculture. He has been much in demand for conferences, scientific review boards and interviews.
Lindow’s new fame arose because he wanted to put a small amount of a harmless bacteria on a few potato plants in an isolated field in Northern California. That bacterium, however, had been created by genetic engineering, in which the techniques of biochemistry are used to move genes from one organism to another.
Lindow’s effort was blocked for two years by a lawsuit filed by author and activist Jeremy Rifkin of the Washington-based Foundation on Economic Trends. The suit argued that the environmental consequences of the use of the bacterium were unknown. Public fear of that unknown brought colleagues and reporters knocking on Lindow’s door.
The restrictions imposed by that lawsuit were effectively overthrown last February by an appeals court.
The repercussions of the suit are still being felt, however, as the Washington bureaucracy struggles to decide who is going to regulate genetic engineering and how they are going to do it. How that struggle is resolved will have a profound impact on agricultural research for the rest of the century.
The potential stakes are large. Industry sources estimate that the eventual market for microbial pesticides will total $700 million to $900 million per year. The market for improved plant seeds could total several times that figure, especially if, as is hoped, scientists can develop plants that make their own fertilizer.
Scientists also hope to use genetic engineering to produce larger animals, animals that use their feed more efficiently or animals that produce more young. Most of these applications will require taking a genetically engineered product out of the laboratory and putting it into the farmyard.
Many Others Are Waiting
Even though there are only a small number of researchers and companies that have applied to test genetically engineered products, a much larger number are sitting on the sidelines waiting to see how those applications are handled.
Meanwhile, Lindow, who still occupies a small office in Hilgard Hall, an old campus building with cramped, airless laboratories, simply wants to get on with his research.
The plant pathologist has been working with a common bacterium, Pseudomonas syringae , that is virtually ubiquitous in the environment. It secretes a protein that serves as a nucleus for the formation of ice crystals. In the presence of P . syringae, ice forms at temperatures two to three degrees higher than it would otherwise.
Preventing Frost Damage
For many agricultural crops, two to three degrees can make a big difference. A freeze too early in the growing season or too early in the fall can cause major crop damage. Lindow wants to give farmers a little more breathing space by replacing the naturally occurring bacterium with one that does not secrete the ice-nucleation protein.
He has removed from the bacterium the gene that codes the ice-nucleation protein. He proposes to spray this modified bacterium onto young plants so that they can become established before the naturally occurring bacterial form has a chance. The plants would then be able to survive lower temperatures without damage.
Studies in greenhouses showed that this concept would work. When the bacteria were applied to newly sprouted potato plants, the naturally occurring bacterium could not establish itself on the plants and the plants did not suffer frost damage. Use of the bacterium on crops might thus prevent millions of dollars of damage each year.
Field Test Sought
Lindow then applied to the Recombinant DNA Advisory Committee of the National Institutes of Health to field-test the bacterium at the University of California’s experiment station at Tulelake, Calif., near the Oregon border. The committee approved the test, and he was ready to begin in October, 1983, when Rifkin filed his suit.
That suit charged that National Institutes violated the National Environmental Policy Act by failing to conduct two kinds of analyses of the proposed studies: an environmental assessment and a much lengthier evaluation called an environmental impact statement.
An environmental assessment, required for any federal action, is a concise public document that provides a brief assessment of potential risk. It determines whether an environmental impact statement is necessary.
The impact statement is a much longer, highly detailed assessment of risks and benefits. It requires much more research and extensive consulting with all agencies and groups that may be involved in the project under consideration.
Tests Postponed
When Rifkin threatened to seek an injunction to stop the tests, Lindow and his colleagues decided to postpone them until the spring of 1984. The tests were again delayed, however, when U.S. District Judge John Sirica--of Watergate fame--granted a temporary injunction in May, 1984.
Sirica conceded that neither the research nor the safety was in question. Instead, the decision was based on the legal question of whether National Institutes should have prepared an environmental impact statement before approving the release of genetically engineered organisms into the environment. Lindow was disappointed.
“I was a little surprised to see the suit filed,” he said, “because we thought the study was about as safe as possible. Our real surprise came when the judge upheld it. Everybody thought (the suit) was without merit, and we were surprised that a small, technical, legal consideration was used and held above all the other considerations presented to the court.”
Research Involved
The temporary injunction applied only to research that had been funded in whole or in part by the National Institutes of Health--and, in fact, the institute’s authority to control genetic engineering extends only to research it has funded. Nonetheless, most companies have felt themselves morally bound by the same rules and have sought permission for projects where comparable permission would be required for National Institutes-funded investigators.
Advanced Genetic Sciences Inc. of Oakland had been doing work virtually identical to Lindow’s and had applied to National Institutes for permission to field-test its modified bacterium. Agracetus of Middleton, Wis., also had applied to the institute for permission to field-test genetically modified tobacco plants that had been given disease-resistant traits.
The advisory committee granted permission to both firms. National Institutes Director James Wyngaarden, however, argued that there should be no double standard and delayed both applications until the resolution of the suit. The Oakland firm has since withdrawn its application and submitted it instead to EPA.
‘Disruptive to Work’
While the suit was working its way through the courts, Lindow became an unofficial spokesman--at no small cost to his research. “Certainly it has been very disruptive to our work. It’s maddening to have to give more and more interviews because of the concerns that have arisen.
“(The suit) seemed to give some validity to the suggestions that the experiment was not safe. . . . I would just as soon be anonymous but, at the same time, you can’t hide without looking guilty. So that means taking at least some time to explain what’s happening and to educate the public on what scientists do and the procedures scientists use to regulate themselves.”
His defense of his work is straightforward: “The bacterium we are working with is neither new nor novel to California. The procedure we used to construct it is somewhat novel, but that in itself doesn’t lead to the creation of a novel organism.
Removed a Gene
“The bacterium is a native of Tulelake, and we simply took it to a laboratory and removed one gene, as could have happened in nature by various mutational processes. So we don’t think that simply using a recombinant technique should in itself flag this as creating a dangerous organism.” Earlier this year, the stage apparently was set for him to return to his normal routine. On Feb. 27, the U.S. Court of Appeals for the District of Columbia awarded National Institutes and Rifkin each a partial victory.
The court unanimously upheld Sirica’s moratorium on field tests until an environmental assessment of the Lindow experiment--and any other proposed experiment--was obtained. But it also ruled that the more time-consuming environmental impact statement was not necessary.
Judge J. Skelly Wright, who wrote the decision, had harsh words for the institute: “We emphatically agree with the district court’s conclusion that NIH has not yet displayed the rigorous attention to environmental concern demanded by law. . . .
‘Significant’ Concern’
“The most glaring deficiency in the institute’s review of (the Lindow experiment) is its treatment of the possibility of dispersion of recombinant DNA-containing organisms. An environmental assessment that fails to address a significant environmental concern can hardly be deemed adequate.”
The court also was not kind to Rifkin’s foundation. In a concurring opinion, Judge George MacKinnon wrote: “The foundation’s conduct has also delayed this vital experiment for a very considerable length of time. The use of delaying tactics by those who fear and oppose scientific progress is nothing new.
“It would, however, be a national catastrophe if the development of this promising new science of genetic engineering were crippled by the unconscionable delays that have been brought by litigants. . . .”
Even before the decision was issued, Washington agencies had been involved in a struggle of their own to determine who would regulate materials produced by genetic engineering techniques.
Jurisdiction Claimed
National Institutes, the EPA, the Department of Agriculture, the Food and Drug Administration, the Department of Transportation, the Occupational Safety and Health Administration, and the Centers for Disease Control have all claimed some jurisdiction over genetically engineered products. Only recently has some consensus begun to emerge.
The Recombinant DNA Advisory Committee still has control over all genetic engineering research funded by National Institutes, although other agencies may also have to approve specific products. The Food and Drug Administration has jurisdiction over all human and animal drugs, medical devices and color additives produced by genetic engineering.
The EPA will oversee industrial chemicals produced by genetically engineered organisms, the organisms themselves if they are used commercially or to make chemicals normally regulated by the EPA, and biological pesticides. Lindow and Advanced Genetic Sciences thus need approval from the EPA for field studies.
The Department of Agriculture will regulate animal vaccines and related products made by genetic engineering, imported “chemical substances” and biological pesticides. Each of the agencies has said that the genetically engineered products will be regulated under the same laws that govern similar products produced by conventional means.
Some Gray Areas
Gray areas still exist, however. It is not clear, for example, who has ultimate authority over plants produced by genetic engineering. Agracetus has thus filed applications for its proposed field tests with several agencies on the apparent assumption that one of those will be the right one.
The EPA, meanwhile, has asked Lindow and Agracetus for more information. The scientist, who is gathering the data now, said it will constitute a “very lengthy document.” He hopes to begin field work next spring.
Lindow and the Oakland firm also have been joined by a third applicant, Monsanto Co. of St. Louis. In December, Monsanto applied to the EPA for permission to field-test a genetically engineered microbe that would protect plants from pests such as the corn earworm, tobacco hornworm, the soybean podworm and the black cutworm.
Bacteria in Soil
Monsanto scientists have engineered a common soil bacterium, Pseudomonas fluorescens , so that it secretes an enzyme that degrades the intestines of caterpillars but is harmless to other species.
In practice, corn seeds, for example, would be coated with the modified bacterium before they are planted. As the corn grows, the bacteria would colonize the roots and kill any caterpillar that nibbled on them. Tests in greenhouses show, Monsanto says, that the engineered bacteria survive in the soil only for 10 to 12 weeks.
Monsanto would like to begin selling coated seed as early as 1988, but so far, the EPA’s response has been the same as it was to Lindow and Advanced Genetic Sciences: Send more data. “We’re all three in the same boat,” says Lindow. “Obviously they want to be very thorough before they give the first approval.”
Studies Already Done
There is a certain amount of irony in the EPA’s great attention to detail, as both Lindow and Agracetus have, for all practical purposes, already carried out their studies. They used a naturally occurring variant of P . fluorescens that does not contain the ice-nucleation gene, and found that it worked as predicted.
Why, then, do they need to use the engineered version? Because this is a prototype study, important in itself but with larger implications for the future.
“There are a number of other bacteria that are plant pests that might be controlled in this manner,” Lindow said. “There is, for example, a disease of tomatoes called bacterial speck that is caused by a bacterium called Pseudomonas tomato . We think we can remove the genes that enable it to invade the plant cells and cause damage.
“The technique will probably have its greatest importance for tree crops, which are particularly susceptible to bacterial infection. But to use it most effectively, we have to know precisely how it works. To do that, we need the new bacterium to be as close as possible to the old one. And for that, we need genetic engineering.”
Looking back, Lindow concedes that Rifkin’s suit has had some positive benefit in that it has forced scientists to examine potential environmental effects more closely. Scientists have learned “a lot” about risk, he said, adding, “From that, hopefully, we can go forward with some reasonable expectation that we know what we’re doing.”
