Risk, Regulation, and Biotechnology

...It is as if all the industry were made to dress in space suits, even as they perform the most mundane of tasks and even as onlookers nonTHE AMERICAN SPECTATOR JANUARY 1989 21 chalantly sip their morning coffee and report on the brave new world of biotechnology for the evening news hour...

...There are many reasons why this perceived incompatibility between the emerging field of biotechnology and the regulations that govern it should matter to Americans...

...It is news to no one that the allocation of public resources often has less to do with maximizing the health and welfare of Americans than with responding to regulatory whims and imagined threats to health and safety...

...These questions were raised perhaps most famously in Cambridge, Massachusetts in the spring of 1976, when the city council took the scientists at Harvard University to task for conducting some of the pioneering experiments in genetic engineering without first informing the community...

...In what may be the ultimate irony of the sad story of the destruction wrought by Dutch Elm disease in this country, Strobel's trees, too, were arrested for resisting arrest...

...If worse comes to worst, we could have a major disaster on our hands...

...To translate, he was guilty of breaking rules designed to protect the environment even though he wasn't actually endangering the environment...

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...Why she was made to wear such a ridiculous getup is anyone's guess, since of course if the bacteria was ruled safe Malcolm Gladwell former assistant managing editor of The American Spectator is a business reporter for the Washington Post...

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...But insulin cloned from humans has turned out to be only marginally more effective—and slightly more expensive—than the purified pig's insulin that had been given to diabetics previously...

...The would-be regulator had missed the mark...

...Apparently not, for his bacterium contained no manmade DNA ligations...

...There is nothing wrong with the questions that Velluci and many since his time have raised in response to the biotechnology revolution...

...EPA's regulatory approach is at odds with the philosophy adopted by the FDA, USDA, National Science Foundation, and National In-stitutes of Health, as well as the government's position at the OECD [Organization of Economic Coordination and Development]," one of the industry's trade associations said in a statement last summer...

...Did they apply to Strobel...

...As of the June 26, 1986 Federal Register, pages 23302-23393, the EPA has its own rules and Strobel's test fell within them...

...But Strobel assumed that the EPA followed the NIH's general guidelines for outdoor tests, but that is no longer true...

...But there has always been a sense that in someway the public perception of what biotechnology is, and what kind of regulations are required to control it, are out of sync with the actual risks presented by the technology itself...

...By the time small start-up companies began to form in the early 1980s to exploit the new technologies, to discover new drugs, or to create new strains of agricultural crops, biotechnology was a magic word among investors...

...But the gist of the whole affair was always crystal clear...

...Velluci, a populist type who once proposed solving the Cambridge parking problem by paving over Harvard Yard, made repeated references to Frankenstein during the debate, as a way of expressing his fears over the possible outcome of experiments then underway in the Harvard biology department to clone the human gene for insulin...

...Had the experiment been a failure, there would have been no clump of trees for investigators to discover, and no evidence of Strobel's apparent crime...

...A common bacteria modified by the tools of genetic engineering was sprayed on strawberry plants to protect them against frost...

...Strobel was also punished even though almost no one believed that the bacterium he was injecting into his trees posed any general threat to the environment...

...Without patents, the industry made clear, the commercialization of animal research would simply go forward by other means: technological advances once made public would be kept as trade secrets, or buyers would be bound by legal contracts to respect intellectual property that the patent law would not...

...Or return it and you owe us nothing...

...At the moment the stakes are simply strawberries that survive the nip of frost and a reprieve for the country's elm trees...

...In the area of agriculture, biotechnology probably will bring dramatic changes—bigger and more productive farm animals, more effective and environmentally sound pesticides, improved crop strains with larger yields...

...There were calls by some of his peers for the "book" to be thrown at him for recklessly endangering the public safety, and the clump of trees on which he performed his experiment was summarily cut down and burned...

...Then there are general principles laid down by the National Institutes of Health.defining what is and what is not an experiment worthy of regulation...

...The risks associated with the introduction of R-DNA engineered organisms are the same in kind as those associated with the introduction into the environment of unmodified organisms and organisms modified by othergenetic techniques," a National Academy of Sciences panel stated in a white paper a year and a half ago...

...And when the Environmental Protection Agency found out that Strobel had conducted his test without clearing it with the agency first and having its environmental impact reviewed by a panel of experts, he was sharply reprimanded and a year-long restriction on his research activities was imposed...

...But the rational connection between the group's disquiet over animal research and their calls for a patent moratorium was never clear...

...What will happen then...

...From the beginning, the highest of claims were made for the new powers that were suddenly at the disposal of scientists...

...But there may come a time when biotechnology moves beyond these early experiments to more profound manipulation of plant and animal life...

...Biotech's regulatory problem is the product of the extraordinary expectations that have been swirling around the industry since the first human gene was synthesized and cloned more than a decade ago...

...But when word of the release came back to CGI's heavyweight panel on social responsibility, Ruckelshaus and three others on the committee quit, along with the company's lawyer...

...It is as if the public that has greeted the fruits of this new science and the researchers and tiny companies that have spawned it were somehow speaking in a different language...

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...The cliche that all of our lives may someday be touched by biotechnology may or may not be true, but it is certainly the case that what is now a small industry will someday be a large one, and whatever impediments are placed on the growth of U.S...

...I t is not that the biotech industry feels its attempts to seek practical applications for the products of the laboratory have been overregulated...

...Before any group of scientists can introduce some new creation into the world, they have to comply with a series of stringent and often confusing regulations involving two or even three separate government agencies...

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...Besides, isn't that what genetic engineers are attempting with plants and other living organisms—transferring the genes of one to another, modifying the structure of life forms to suit changing environmental conditions—the same thing that has always been done by other means by scientists and farmers and indeed nature itself...

...Other promising cloned proteins are more cost effective than insulin or TPA, but few—at this point anyway—are the miracle drugs that genetic engineering was to bring to the benefit of Americans...

...But coming after five years of controversy and regulatory review, after lawsuits from angry environmentalists and hostile ordinances from local city councils, it represented a milestone in the history of the biotech industry: for the first time the government had given its imprimatur to the fruits of gene manipulation...

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...As well, it was not until last summer that the National Academy of Sciences and the Congressional Office of Technology Assessment weighed in with reports downplaying some of the concerns that had inhibited the EPA...

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...Such efforts are deemed necessary in spite of overwhelming evidence that what is being created by the biotech industry is no more troubling or dangerous than the work with improving crops and chemicals that has gone on for years before...

...Strobel was able to cut down and burn his trees in the wake of the EPA investigation only because the bacterium with which he hadinoculated them had kept them alive...

...But on closer examination, the so-called agricultural revolution is no more a revolution than biotech's entry into the pharmaceutical world...

...Some of the scientific and technological problems that our nation faces are extremely difficult to handle," Strobel told the Senate...

...Patent Office in early 1988 first granted a patent for a genetically altered animal, the decision raised a storm of protest and calls for a moratorium on animal patents from some religious leaders, legislators, and biotechnology's traditional critics in the environmental community...

...There was nothing untruthful about the CGI press release...

...There must also be a careful assessment of how the risks involved with biotechnology compare with the risks inherent in the methods and technology it replaces, howgenetically engineered pesticides match up against chemicals that contaminate groundwater and lay waste to lab rats...

...As he would say later, "You almost have to be a lawyer before you can be a scientist...

...The debate about biotechnology, as essayist Lewis Thomas wrote in the New England Journal of Medicine some years ago, "has become an emotional issue, with too many irretrievably lost tempers on both sides...

...Small-scale field tests are likely to be the only way potential risks from commercial-scale uses of genetically engineered organisms can be evaluated...

...In fact there is general agreement that the broad expanse of unexplored territory opened up by biotechnology demands some sort of close scrutiny...

...It did not extend to making the world safe for birds...

...One biotech firm in Maryland, Crop Genetics International, was so nervous about how its applications for testing a bio-engineered corn pesticide would be treated by the authorities that it spent close to $8 million conducting safety tests and signed former EPA Chief William Ruckelshaus, eminence WRITERS AND RESEARCHERS: LEND US YOUR MESSY DESKS, CLUTTERED DRAWERS, AND STUFFED BRIEFCASES FOR JUST 8 MINUTES A DAY...

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...As the EPA officials responsible for disciplining Strobel said, in a kind of grand bureaucratic doublethink, the decision to punish him was based upon his "failure to comply with agency regulations and policies, rather than because of any adverse effect this experiment may have...

...In some cases the proposals suggested that scientists conducting tests be required to answer no less than thirty-five questions to the satisfaction of the EPA before being permitted to go ahead with research...

...T here are other areas, beyond the 1. question of releasing genetically engineered organisms, where the regulation of biotechnology has appeared to turn more on emotional and political issues than on an accurate perception of risk...

...This was a tool, the public was told, that would transform the world...

...For not being familiar with that redefinition, Strobel was punished...

...Even as the EPA was suggesting that some oversight responsibility be delegated to local safety committees last summer, they were also drafting a new set of strict regulations covering a different category of tests involving the use of genetically engineered micro-organisms under the Toxic Substances Review Act...

...He was arrested for resisting arrest...

...Alongthe way, if their bacterium is classified by the U.S...

...In the twenty months since the Advanced Genetic Science's field test, a handful of other biotechnology companies have received the federal go-ahead to take their experiments out of doors...

...In short, while the arguments made by biotech's critics about the unanswered moral questions raised by pressing forward with genetic research with animals may well be sound, the expression of that concern was not...

...At the same time the promises made on behalf of the new science attracted an active group of critics, regulators, environmentalists, and concerned citizens The picture taken on April 24, 1987, of Julianne Lindemann walking through the strawberry fields of northern California has come to take on a strange and special significance...

...After years of being cast as mad scientists, the AGS test meant that the biotechnology industry had finally gained acceptance...

...And if this new science will someday have an impact on all of society, then shouldn't all of society have a say in how it is developed...

...Not so, he found out...

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...This isn't to say that someday the ability to take natural substances, to copy them, or to manipulate their genetic makeup, or even to create new life forms entirely, won't profoundly alter American society and require stringent oversight to protect the public from undue environmental risk...

...What this says about the state of biotech regulation, however, is already painfully clear...

...24 THE AMERICAN SPECTATOR JANUARY 1989...

...The Department of Agriculture has rules about outdoor tests...

...at worst we may have fashioned a system that both frustrates the growth of this promising technology and exposes the public to more dangers than would otherwise be the case...

...Or, as one letter to a Cambridge newspaper on the Harvard debate put it: "We are amazed that anyone should express concern about the creation of a laboratory at Harvard to experiment with new life forms...

...At worst it was impolitic, pointing out an uncomfortable truth about the environmental toll that chemically based agriculture takes on the environment...

...In most cases, for example, the organisms being created and cloned are actually only mild variations of micro-organisms that already exist in the environment...

...Indeed, the evidence is just as overwhelming that the toll taken by such oversight in time and money may be curtailing the growth of the industry itself...

...But even today, almost two years after the fact, there are those who will say that the effect of that picture, burned into the collective consciousness the following day on TV screens and newspapers around the world, was to contradict the entire exercise, to perpetuate the superstition that gene splicing was a strange and dangerous science to be carried out only under the most extreme precautions...

...What would happen, after all, if Mayor Velluci and his visions of Frankenstein were on a local bio-safety committee...

...T he way the regulations governing 1 biotech tests currently stand, companies and researchers must apply to the EPA first for permission to conduct a small scale, one- or two-acre experiment...

...By some whim of the California health authority, Lindemann was made to wear what appeared to be a space suit, as if the bacteria she was spraying was radioactive, or as if the field on which she stood was the surface of the moon...

...Here in a country where there are thousands of toxic waste dumps and where millions of tons of chemicals are dumped on American cropland every year in the name of better agriculture, a man had his work destroyed for trying to find a cure for Dutch Elm disease without a permit...

...Still, with biotechnology, there seems to be a special imperative to decipher just where the true risk lies, and what it is the public deserves to be protected from...

...The solution for biotechnology obviously must lie with more careful collection of data and gradual lifting of the regulatory umbrella as the risks become better known...

...More importantly, however, how the emerging field of biotech is treated by the public and the appropriate authorities is a test case for how any new technology is greeted by society...

...enough to be released into the environment then it was surely safe enough to be released by a scientist dressed like a normal human being...

...22 THE AMERICAN SPECTATOR JANUARY 1989 who saw in the claims made for biotechnology a series of unanswered questions: How safe is it to introduce genetically improved, manmade organisms into an environment that has evolved over millions of years...

...What the EPA proposed was that federal oversight be extended to categories of commercial and industrial uses of micro-organisms that had not previously been covered by regulations...

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...D iotech's regulatory problem is the product of the extraordinary expectations that have been swirling around the industry since the first human gene was synthesized and cloned more than a decade ago...

...Some have had to defend their rights to conduct experiments in court against skeptical environmentalists, and at the very least to conduct extensive public relations campaigns to convince local communities that the genetically improved seeds or manmade micro-organisms conceived in a test tube will not run amok when released into the environment...

...Crop Genetics and Advanced Genetics Sciences and the other biotech firms, in requesting permission to test, so far have been pioneers, presenting the EPA with an entirely new set of questions and problems...

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...Because the bacterium had been modified slightly by genetic means to make it more effective against the deadly Dutch Elm fungus, this was, for the purposes of federal authorities, a biotechnology experiment...

...Billedas biotech's first blockbuster drug, TPA is in fact only slightly better and much more expensive than traditional chemical remedies for heart attacks...

...Some have been pulled off with a minimum of fuss...

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...The same is true for TPA, another of the early biotech products, a natural anti-blood clot protein that has been copied for use in unplugging blocked arteries in heart attack victims...

...And yet in the world of biotechnology, which in its short ten-year history has not always moved on the most rational of courses, the picture taken on April 24, 1987 of Julianne Lindemann walking through the strawberry fields of northern California has come to take on a strange and special significance...

...Random groups of biologists, thrown together by entrepreneurs without any clear idea about what they would be producing or even when they could produce it, were able to raise millions from venture capitalists and millions more from the stock market entirely on the strength of the magical words genetic engineering...

...On top of this we have imposed a sea of regulatory actions by a myriad of federal agencies with conflicting definitions...

...Perhaps worse, he became the target for all those nervous about biotech's future...

...To be fair, the situation can only improve...

...Strobel's Dutch Elm disease vaccine was a bacterium found on various leaves around the world and modified so that it could be injected into elm saplings...

...While chemical companies have for years been able to test their pesticide prototypes without government approval, two of the early proposals for tests of genetically engineered bacteria were rejected by the EPA, despite what the industry said was overwhelming evidence of the tests' safety...

...T t is inconceivable, of course, that one photograph could alter the direction of an entire industry, especially when it depicts nothing more than a woman walking through a strawberry patch...

...It bears mentioning, although few bothered to at the time, that Strobel's experiment—at least in its preliminary stages—was a success...

...And because nature is already so diverse, GEMs will not likely add significant amounts of genetic variation to the environment...

...They have had to do more than their successors will...

...But the picture ruined everything...

...Did they apply to Strobel...

...To be sure, the variations created by genetic engineering on these familiar micro-organisms are entirely new...

...Some of the experiments have encountered the same degree of controversy as that first experiment...

...They too have said that their efforts have become the subject not of too much scrutiny but of scrutiny that has missed the mark...

...Several months later Strobel was brought before the Senate to testify about his act of disobedience and about the new possibility of reform...

...But all in some way have fallen under the shadow of that first test in a California strawberry patch...

...The industry, though clad in a ridiculous space suit, was lumbering on...

...In June of that year, Strobel independently injected a small group of elm trees on the MSU campus with a natural bacterium that has proved effective in protecting trees in the laboratory against Dutch Elm disease...

...In a press release last spring, for example, Crop Genetics International, the Maryland company with a new idea for protecting corn from caterpillar infestation, pointed out that one of the advantages of a genetically engineered corn pesticide was that the chemical currently used to protect corn from caterpillars has the unintended side effect of killing 2.5 million birds annually, among them the endangered bald eagle...

...A number of biotech firms have begun experiments attempting to protect corn plants from their biggest pest—a caterpillar known as the European corn borer—using modified versions of a bacterium that is already used in another form as a pesticide...

...With any new advance comes a necessary comparison of the risks presented by the new against the risks associated with the old, and the advantages of what is coming against what is already there...

...But many scientists stress that what is new isn't necessarily harmful, although it may raise a series of legitimate and sometimes difficult questions...

...This is a serious matter," said Cambridge mayor Alfred Velluci at the time...

...On that day a small West Coast biotech firm—Advanced Genetic Sciences—became the first company ever to receive government approval to take a manmade organism out of the laboratory and release dt in the open air...

...There were rumors subsequently that the company that makes the pesticide had put pressure on Crop Genetics, and that some members of the committee had important ties to the chemical industry they wished to protect...

...To date, the biotech community has faced most of its difficulty in passing the first step of this review process...

...Like so many others who have weighed in on the biotech debate over the past few years, Ruckelshaus and company's sense of social responsibility extended to making biotech safe for the world...

...It has lost the sound of a discussion of technological safety, and now begins to sound like something else, almost like a religious controversy . . ." There is nothing especially unique about this kind of public policy debate in American life, of course...

...The OTA was particularly blunt: "None of the small-scale field tests proposed or probable within the next several years are likely to result in an environmental problem that would be widespread or difficult to control...

...To begin with, the rule he defied in not registering his test with the authorities is less a single standard than one part of a confusing patchwork of three separate sets of rules...

...Not even the government itself can decide what kind of risk is posed to the environment by genetic engineering...

...But in this, the biotech industry has not always been successful...

...The first human protein to be identified and cloned was insulin, which was then re-administered to diabetics...

...But for the moment much of the furor over biotech is over a technological straw man...

...The problem is that the revolution itself isn't really a revolution at all, and that the claims that many of the new technology's critics have responded to have had more in common with the industry's press releases than with reality...

...Even the EPA itself has now suggested that at some time in the near future, the go-ahead for field tests should be given entirely by community-based bio-safety committees, instead of being reviewed centrally by the EPA office in Washington...

...This is true not just of the few dozen firms that have used the techniques of genetic engineering to improve crop agriculture but also those who are looking to improve livestock, to develop stronger and more useful strains of domestic animals...

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...A look around Harvard Square at nearly any time of day or night reveals life forms sufficiently grotesque to convince us it is already too late for such protest...

...Some industry officials worry that this would simply make regulation more capricious, with parts of the country less convinced of the merits of biotechnology and making life worse for the industry than it was under the previous system...

...For example, the OTA and some federal authorities have given their blessing to small-scale experiments...

...Finally, the EPA has jurisdiction over some types of outdoor experiments...

...Still, it is not clear that the problems that have surrounded biotech regulations are entirely over...

...But how will regulators react when a biotech firm wants to jump from a relatively innocuous one-acre test to an experiment covering several hundred acres...

...And is throwing responsibility for approving tests to community-based safety committees really an advance...

...I n the area of drug research, for ex- 1 ample, biotech's big breakthrough has been to use the body as a pharmacy, locating natural human proteins with therapeutic value, cloning them, and then re-introducing them to the body as drugs...

...The rules are still under discussion and in fact prompted a fierce summer-long battle between the EPA and opponents of the rules throughout the federal bureaucracy, who claimed that the EPA was attempting to extend regulations to cover work that did not even remotely pose any safety or environmental threats...

...Strobel's was smaller than that...

...Even the much ballyhooed bacterium sprayed on the California strawberry field is of a family of bacteria that have been protecting plants from frost for millions of years...

...And as if the injustice of the image was not enough, they will also point to the gathered crowd of reporters and onlookers just a few feet behind Lindemann in the picture, munching on donuts, sipping coffee, and snapping away with cameras without any kind of protective gear at all...

...at best it may be too soon to make that determination, as the regulatory wheels in Washington are still grinding...

...firms will inevitably end up as advantages for the Japanese or the Germans or the British or whomever our competitors may someday be...

...T here are other issues that continue to plague the biotech industry...

...Consider the questions Strobel had to answer before beginning his war on Dutch Elm disease...

...It is impossible to read his testimony without getting a sense of his indignation...

...According to principles developed by Harvard's Bernard Davis, genetically engineered micro-organisms (GEMs), like domesticated farm species, are not particularly apt to outsurvive unmanipulated species already present in an environment...

...There are several points worth making about Strobel's crime and punishment...

...F ew stories better demonstrate the problems inherent in the present regulatory system than that of Gary Strobel, the Montana State University researcher who ran afoul of the public and regulatory authorities in the summer of 1987...

...It was a simple experiment...

...In the case of using bacteria to control a plant disease, USDA rules apply only to test sites of over ten acres...

...It is not clear that with biotechnology this has been done with any accuracy...

...Box 228, Somerville, MA 02143 THE AMERICAN SPECTATOR JANUARY 1989 23 grise Elliot Richardson, and Bush adviser Robert Teeter to a special "Committee on Social Responsibility" to convince federal regulators of their commitment to playing by the rules...

...Department of Agriculture as a "genetically engineered plant pest," they would have to get approval from that agency, as well as inform the National Institutes of Health of their activity...

...A patent, after all, is simply one of a number of legal tools an inventor can use to protect the fruits of his labor...

...And then, if that test is judged to have been ecologically acceptable—not threatening the existing eco-system or spreading beyond the target site—the EPA grants a permit for a full-scale experiment...

...The entire effect is one that is absolutely impossible for a scientific researcher (especially one in a small business or academic institution) to comprehend and to follow on a regular basis . . . . As one who has suffered the consequences of this complex system I feel that the time has come for sweeping changes in how we think about biotechnology and how we regulate it...