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Biotechnology and its public
OKa-791X/s4$3.00 + .oo Copyright 0 1984 Pergamon Press Ltd
TecbnoLo~l~ Sociefy, Vol. 6. pp. 17-21(1984) Printed in the USA. All tights tcsctwd.
Biotechnology and Its Public Nicholas Wade
ABSlXACT. The autbqr prvviah a perspective on three hey area of biotechnology: the public debate over hazards, tbe comme&iization of the technology, and etbica/ hues that are king in terms of apphati~n of genetic therapy to humans. He reviews tbe biztory of tbe recombinant DNA reseasb debate beginning at Asiiomar in 1975, when the molcc&r biologtits calied for a temporary moratorium on certain expetiments, so the NIH might develop gui&/ines to govern this reseamb. The autbor tben cbaracterkes tbe lobbying acthitiks of the bio/ogiss against proposed rcguhtion at the feakrai, state and iocal Ieve/. Despite the lobbying, be conchdes that Congress did not enact iegtkkion because of the exempiary behavior of tbe biologists, beginning with their meeting at Asiiomar. The author next &sc?ibes the impact commehhation of tbaktecbndogy u&Yhave on ti biologtits wbo traditionally have not been invofved in tbat press (as have cbemtkts and pbysicirt). He a/so comments on tbe etbks of biotechnology, con&ding tbat the more powe$d biology becomes, the more its uses and some contn9 of those uses u&Ube &bated
Biotechnology has opened up large cracks in the high wall that shields the laboratory from public gaze. The public already understands that, in genetic engineering, today’s research discovery may be tomorrow’s new product. Biologists’ conduct of their affairs will probably come under closer public scrutiny than any group of rescarchcrs has faced hitherto. In meeting that test, they have both assets and handicaps. A vivid indication of public interest in biology was the statement issued in June 1983 by a wide spectrum of Protestant, Catholic and Jewish leaders. The group called for a ban on making inheritable changes to the human genome. Since its members represented the heads of most major denominations in the United States, the statement served at the least as a warning of the kind of debate that biotechnology is likely to engender.
Biology ‘JPublic Standing
Despite quite frequent assertions to the contrary by some scientific spokesmen, the public holds science in high regard. The biennial surveys conducted for the National Science Board and published in its Science Indicators series consistently portray strongly favorable attitudes toward science, and demonstrate the public’s ability to distinguish between science and the adverse effects of certain technologies. Biologists capitalized on this goodwill during the late 1970s by themselves raising and addressing the issue of recombinant DNA hazards. Provided that at least a 17
18
Ni&&s
Waak
figleaf of the original safety rules is kept in place, that self-denying posture will serve to argue that biologists can continue to be trusted to run their own affairs. The question of the autonomy of science will be a critical issue for biologists and the public in the years ahead. For exactly 20 years, from the discovery of the structure of DNA in 1953 to the invention of gene-splicing in 1973, molecular biologists enjoyed the luxury of working in decent obscurity. During that long and fecund gestation, the groundwork of a powerful discipline was laid. A large body of theory was established about the molecular biology of viruses and bacteria, even if cukaryotcs continued to remain intractable. New and more powerful techniques were devised. Besides the recombinant DNA technique itself, there were the two methods of rapid DNA sequencing developed by Sangcr and by Maxam and Gilbert. Kiihler, working in Milstcin’s laboratory, invented the monoclonal antibody technique in 1975. The citizens of the United States and Europe, benevolent patrons who paid for these good works, had given rather little attention to what was being done with their money. When their attention was drawn to molecular biology by the debate over the hazards of gene-splicing, they viewed the new science as though seeing it for the frrst time. Like Athena springing from the head of Zeus, molecular biology was born fully grown. The public’s first impressions were favorable. Here were the midwives of the new science already debating in advance of any danger how a powerful new tool could best be wielded so as to do the public no harm. The debate burst into public view with the convening of the Asilomar conference of 1975. What prompted the conference was a chain of events that began when Robert Pollack, then of Cold Spring Harbor, learned of an experiment in which it was planned to insert SV-40 virus into Eschcrichia coli, the leading denizen of the human gut. Some biologists with no sense of history have argued that the cxpcrimcnt was always clearly harmless, and that, if only they had been consulted at the time, they would have said so. In fact, the hazard posed by the experiment was so novel, and crossed the demarcation lines of so many different disciplines, that no single expert in 1971 was qualified to answer Pollack’s objection. The Asdomar Conference The Asilomar conference laid the basis for addressing that issue, and biologists deserve enduring credit for denying themselves full use of the new technique that everyone was impatient to use. But a few spots began to appear on the stainless record after 1976, when the National Institutes of Health issued its recombinant DNA safety rules. Up to that point, the possible hazards of the technique had been freely discussed among scientists. But when Congress and local communities began their own discussions of whether the safety rules were adequate, as they had a perfect right to do, the tenor of the debate changed abruptly. The dissent from within the scientific community evaporated overnight. An opinion poll taken by The Boston Globe showed that many biologists seriously doubted that the NIH safety rules were stringent enough, and yet, with honorable exceptions such as Ernest Chargaff and Robert Sinshcimcr, few voiced their concern
Biotechiogy md Its Public
19
in public. The young researchers who had vocally protested the laxity of the earlier versions of the safety rules fell suddenly silent. They claimed, whether rightly or wrongly, to be under great pressure from their elders to say nothing to rock the boat or entice politicians to bring research under tighter control. Free and open debate is the heart of science. What prompted biologists to abandon this central value was fm: fear that the public would fail to understand the hazard issue, would demand absolute safety and, worst of all, might intrude an alien presence into the laboratory itself, demanding a veto over every proposed experiment . Events proved that fear to be misplaced. Both in Congress and at the local level, as with the Cambridge citizens council, the public proved to be both understanding of the biologists’ concerns and tolerant in its recommendations. Throughout the political debate, scientific lobbyists kept protesting that the public didn’t seem to trust scientists. The truth was just the opposite: It was scientists who didn’t trust the public. True, Congress played for a time with the outrageous notion of writing a law that scientists should abide by the safety rules that they themselves had written. This gross affront to the dignity of the scientific profession elicited vehement reflexes. The Bag of Galileo was waved con brie. Congress was accused of embarking on a Lysenkoist crusade to hobble genetics and stamp out freedom of inquiry. Opponents were castigated for the extremism of their arguments. This show of &ontcd dignity was somewhat undercut by the discovery that biologists at two leading institutions, the University of California, San Francisco, and the Harvard Medical School, had indeed been unable to abide by the safety rules. The infractions, though minor, were highly inopportune. Biologists at UCSF, told by NIH that a certain plasmid was not certified for use, went ahead and used it anyway. Entries in the lab’s logbook were falsely recorded. When the incident came to the attention of the department’s biohazard committee, a lukewarm investigation cited the NIH as chief culprit. The infraction at the Harvard Medical School was committed by a biologist who, as a member of the NIH recombinant DNA committee, had himself helped to draw up the regulations. Deputiures jFom the Scientt~c Ethos Had Congress held an ounce of malice toward science or scientists, these manifestations of indiscipline would have furnished ample pretext for imposing draconian rules on research and a roster of fines and forfeits. In fact, Congress’s reaction was astonishingly mild, and in the end it was content merely to exercise oversight without passing any legislation. Biologists, of course, had every right to lobby against legislation they didn’t like. But there were disconcerting departures from the scientific ethos in some of the measures used in the lobbying campaign. Experiments with little real relevance to safety were announced to the press before publication and their sign&ance was grossly overplayed. Political lobbyists routinely use information this way; couldn’t scientists, even in the heat of the moment, have held themselves to a slightly higher standard?
20
Ntihofas Wad..
Similar methods were in evidence as biologists put pressure on the NIH to reduce the stringency of the safety rules. Conferences would be held at which interested experts would pooh-pooh the possible risks of recombinant DNA. Typically there would be little new evidence beyond that which the NIH Recombinant DNA Committee had already considered in drawing up its rules. But the “consensus” of experts would be cited as proof that the rules should be rolled back in this area or that. The condusions of one of these meetings, the Falmouth conference, notes Sheldon Krimsky in his book, Gene& Alchemy, “were extended far beyond their original intent. Even the highly restricted scope of these conclusions . . . is not based on extensive data or rigorous argument; it was reached on the plausibility of the evidence. ” But these were small blemishes on the shining escutcheon of Asilomar. With or without legislation, with tight or relaxed safety rules, biologists had established so responsible a reputation that the next phase of their interaction with society, the commercialization of molecular biology, attracted rather less scrutiny than it probably deserved. The Commemdilzatibn
of Mo/ecu&r Biology
Until recently, molecular biologists disdained reaping financial rewards from pure research. Cohen and Boyer at first neglected to patent the recombinant DNA technique they invented; when urged by the Stanford University patent officer to do so after he had read an account of the invention in The New Yod Times, the two reluctant inventors agreed to apply for a patent only on the condition that any royalties be turned over to their respective institutions. Some argue this attitude was naive; chemists and engineers have been consulting for industry for years. Nonetheless, it represented a widely held attitude among biologists at the time. Since then, there has been an almost complete reversal of views. Biologists en marsc have formed commercial ties with industry or set up their own companies. What is disturbing about this development is its scale. “It is already apparently true that there is no notable biologist in this field anywhere in America who is not working in some way for a business. I interviewed some two dozen of the best molecular biologists in the country and found none,” wrote U%.rhington Post reporter Philip Hilts in 1982. The heavy involvement of biologists in commercial applications deprives the public, at least for the moment and maybe longer, of an independent source of advice. Certainly, if the DNA hazards debate were to be replayed, or resumed, biologists who denied the risk would be accused of self-interest and their arguments discounted. Beyond that, the widespread commercial interests of all leading practitioners cannot fail-despite their individual denials- to have some impact on the overall direction of research, probably shifting it toward practical goals at the expense of knowledge for its own sake. Engineers, of course, see nothing wrong with that; in their discipline many advances have come from tackling applied problems. But biology is not necessarily the same. Not only may the direction of research be shifted, but also the tradition. Harriet Zuckerman’s study of Nobel Prize winners brings to light how many Nobel-
Biotecbnoiogy and Its Public
21
ists received their training at the hands of other Nobelists. What kind of research tradition will be inculcated into today’s crop of graduate students by professors who arc all engaged in pursuing money as well as truth? Perhaps the present high degree of commercialization of academic biology is merely a temporary phase. Perhaps the applied side of molecular biology will bccome sufficiently divorced from pure research that the same individuals will not be in such heavy demand for both activities. More likely, biologists, having once tasted riches, will not retreat to the cloister or resume their vows of poverty. A Third Phase of Debate What will that do to their public image? After hazards and commercialization, a third phase of debate has just begun, that of the ethics of biotechnology. Biologists have not so far established particularly striking credentials in this arena. The first attempt to apply genetic therapy to humans was undertaken by Martin Clint of the University of California, Los Angeles, who inserted human globin genes into the marrow cells of patients suffering from beta-thalasscmia. There was a touch of envy in the criticisms of some of Clint’s colleagues that the experiment was premature; it was in some ways a bold initiative that, in different circumstances, might have drawn praise. Unfortunately, Cline failed to inform fully some five oversight committees as to his intention of performing the cxpcrimcnt. No other genetic therapists have jumped the gun so far, but the ethics of genetic therapy started off on the wrong foot. More serious than this mishap, however, has been an apparent decision by lcading biologists not to participate in the public debate about human genetic engineering, presumably for fear of stirring up an imbroglio similar to that which surrounded the issue of hazard. This tactical decision makes a great deal of sense if, having learned nothing from the past, one believes that an ignorant public is safer than one in a position to give its informed consent. Its direct consequence is a climate of opinion in which the entire spectrum of church leadership can sign the statement discussed above that calls for a ban on making any inheritable changes to the human gcnomc.
What is the outlook for the future? It is obvious that the more powerful biology becomes, the more its uses and the control of those uses will be debated. If biologists arc perceived to be using their science for their own ends or abusing public trust, they will inevitably lose part or 211of their autonomy. How much better for everyone if biology were to remain a community of autonomous, independent researchers, untrammcllcd by cxccssivc commercial tics, free to give objective advice to whoever wants it, and interested only in the disinterested pursuit of truth. That’s not the way things arc headed at present, but the admirable sense with which biologists have conducted their affairs hitherto will doubtless prevail in the end.
TecbnoLo~l~ Sociefy, Vol. 6. pp. 17-21(1984) Printed in the USA. All tights tcsctwd.
Biotechnology and Its Public Nicholas Wade
ABSlXACT. The autbqr prvviah a perspective on three hey area of biotechnology: the public debate over hazards, tbe comme&iization of the technology, and etbica/ hues that are king in terms of apphati~n of genetic therapy to humans. He reviews tbe biztory of tbe recombinant DNA reseasb debate beginning at Asiiomar in 1975, when the molcc&r biologtits calied for a temporary moratorium on certain expetiments, so the NIH might develop gui&/ines to govern this reseamb. The autbor tben cbaracterkes tbe lobbying acthitiks of the bio/ogiss against proposed rcguhtion at the feakrai, state and iocal Ieve/. Despite the lobbying, be conchdes that Congress did not enact iegtkkion because of the exempiary behavior of tbe biologists, beginning with their meeting at Asiiomar. The author next &sc?ibes the impact commehhation of tbaktecbndogy u&Yhave on ti biologtits wbo traditionally have not been invofved in tbat press (as have cbemtkts and pbysicirt). He a/so comments on tbe etbks of biotechnology, con&ding tbat the more powe$d biology becomes, the more its uses and some contn9 of those uses u&Ube &bated
Biotechnology has opened up large cracks in the high wall that shields the laboratory from public gaze. The public already understands that, in genetic engineering, today’s research discovery may be tomorrow’s new product. Biologists’ conduct of their affairs will probably come under closer public scrutiny than any group of rescarchcrs has faced hitherto. In meeting that test, they have both assets and handicaps. A vivid indication of public interest in biology was the statement issued in June 1983 by a wide spectrum of Protestant, Catholic and Jewish leaders. The group called for a ban on making inheritable changes to the human genome. Since its members represented the heads of most major denominations in the United States, the statement served at the least as a warning of the kind of debate that biotechnology is likely to engender.
Biology ‘JPublic Standing
Despite quite frequent assertions to the contrary by some scientific spokesmen, the public holds science in high regard. The biennial surveys conducted for the National Science Board and published in its Science Indicators series consistently portray strongly favorable attitudes toward science, and demonstrate the public’s ability to distinguish between science and the adverse effects of certain technologies. Biologists capitalized on this goodwill during the late 1970s by themselves raising and addressing the issue of recombinant DNA hazards. Provided that at least a 17
18
Ni&&s
Waak
figleaf of the original safety rules is kept in place, that self-denying posture will serve to argue that biologists can continue to be trusted to run their own affairs. The question of the autonomy of science will be a critical issue for biologists and the public in the years ahead. For exactly 20 years, from the discovery of the structure of DNA in 1953 to the invention of gene-splicing in 1973, molecular biologists enjoyed the luxury of working in decent obscurity. During that long and fecund gestation, the groundwork of a powerful discipline was laid. A large body of theory was established about the molecular biology of viruses and bacteria, even if cukaryotcs continued to remain intractable. New and more powerful techniques were devised. Besides the recombinant DNA technique itself, there were the two methods of rapid DNA sequencing developed by Sangcr and by Maxam and Gilbert. Kiihler, working in Milstcin’s laboratory, invented the monoclonal antibody technique in 1975. The citizens of the United States and Europe, benevolent patrons who paid for these good works, had given rather little attention to what was being done with their money. When their attention was drawn to molecular biology by the debate over the hazards of gene-splicing, they viewed the new science as though seeing it for the frrst time. Like Athena springing from the head of Zeus, molecular biology was born fully grown. The public’s first impressions were favorable. Here were the midwives of the new science already debating in advance of any danger how a powerful new tool could best be wielded so as to do the public no harm. The debate burst into public view with the convening of the Asilomar conference of 1975. What prompted the conference was a chain of events that began when Robert Pollack, then of Cold Spring Harbor, learned of an experiment in which it was planned to insert SV-40 virus into Eschcrichia coli, the leading denizen of the human gut. Some biologists with no sense of history have argued that the cxpcrimcnt was always clearly harmless, and that, if only they had been consulted at the time, they would have said so. In fact, the hazard posed by the experiment was so novel, and crossed the demarcation lines of so many different disciplines, that no single expert in 1971 was qualified to answer Pollack’s objection. The Asdomar Conference The Asilomar conference laid the basis for addressing that issue, and biologists deserve enduring credit for denying themselves full use of the new technique that everyone was impatient to use. But a few spots began to appear on the stainless record after 1976, when the National Institutes of Health issued its recombinant DNA safety rules. Up to that point, the possible hazards of the technique had been freely discussed among scientists. But when Congress and local communities began their own discussions of whether the safety rules were adequate, as they had a perfect right to do, the tenor of the debate changed abruptly. The dissent from within the scientific community evaporated overnight. An opinion poll taken by The Boston Globe showed that many biologists seriously doubted that the NIH safety rules were stringent enough, and yet, with honorable exceptions such as Ernest Chargaff and Robert Sinshcimcr, few voiced their concern
Biotechiogy md Its Public
19
in public. The young researchers who had vocally protested the laxity of the earlier versions of the safety rules fell suddenly silent. They claimed, whether rightly or wrongly, to be under great pressure from their elders to say nothing to rock the boat or entice politicians to bring research under tighter control. Free and open debate is the heart of science. What prompted biologists to abandon this central value was fm: fear that the public would fail to understand the hazard issue, would demand absolute safety and, worst of all, might intrude an alien presence into the laboratory itself, demanding a veto over every proposed experiment . Events proved that fear to be misplaced. Both in Congress and at the local level, as with the Cambridge citizens council, the public proved to be both understanding of the biologists’ concerns and tolerant in its recommendations. Throughout the political debate, scientific lobbyists kept protesting that the public didn’t seem to trust scientists. The truth was just the opposite: It was scientists who didn’t trust the public. True, Congress played for a time with the outrageous notion of writing a law that scientists should abide by the safety rules that they themselves had written. This gross affront to the dignity of the scientific profession elicited vehement reflexes. The Bag of Galileo was waved con brie. Congress was accused of embarking on a Lysenkoist crusade to hobble genetics and stamp out freedom of inquiry. Opponents were castigated for the extremism of their arguments. This show of &ontcd dignity was somewhat undercut by the discovery that biologists at two leading institutions, the University of California, San Francisco, and the Harvard Medical School, had indeed been unable to abide by the safety rules. The infractions, though minor, were highly inopportune. Biologists at UCSF, told by NIH that a certain plasmid was not certified for use, went ahead and used it anyway. Entries in the lab’s logbook were falsely recorded. When the incident came to the attention of the department’s biohazard committee, a lukewarm investigation cited the NIH as chief culprit. The infraction at the Harvard Medical School was committed by a biologist who, as a member of the NIH recombinant DNA committee, had himself helped to draw up the regulations. Deputiures jFom the Scientt~c Ethos Had Congress held an ounce of malice toward science or scientists, these manifestations of indiscipline would have furnished ample pretext for imposing draconian rules on research and a roster of fines and forfeits. In fact, Congress’s reaction was astonishingly mild, and in the end it was content merely to exercise oversight without passing any legislation. Biologists, of course, had every right to lobby against legislation they didn’t like. But there were disconcerting departures from the scientific ethos in some of the measures used in the lobbying campaign. Experiments with little real relevance to safety were announced to the press before publication and their sign&ance was grossly overplayed. Political lobbyists routinely use information this way; couldn’t scientists, even in the heat of the moment, have held themselves to a slightly higher standard?
20
Ntihofas Wad..
Similar methods were in evidence as biologists put pressure on the NIH to reduce the stringency of the safety rules. Conferences would be held at which interested experts would pooh-pooh the possible risks of recombinant DNA. Typically there would be little new evidence beyond that which the NIH Recombinant DNA Committee had already considered in drawing up its rules. But the “consensus” of experts would be cited as proof that the rules should be rolled back in this area or that. The condusions of one of these meetings, the Falmouth conference, notes Sheldon Krimsky in his book, Gene& Alchemy, “were extended far beyond their original intent. Even the highly restricted scope of these conclusions . . . is not based on extensive data or rigorous argument; it was reached on the plausibility of the evidence. ” But these were small blemishes on the shining escutcheon of Asilomar. With or without legislation, with tight or relaxed safety rules, biologists had established so responsible a reputation that the next phase of their interaction with society, the commercialization of molecular biology, attracted rather less scrutiny than it probably deserved. The Commemdilzatibn
of Mo/ecu&r Biology
Until recently, molecular biologists disdained reaping financial rewards from pure research. Cohen and Boyer at first neglected to patent the recombinant DNA technique they invented; when urged by the Stanford University patent officer to do so after he had read an account of the invention in The New Yod Times, the two reluctant inventors agreed to apply for a patent only on the condition that any royalties be turned over to their respective institutions. Some argue this attitude was naive; chemists and engineers have been consulting for industry for years. Nonetheless, it represented a widely held attitude among biologists at the time. Since then, there has been an almost complete reversal of views. Biologists en marsc have formed commercial ties with industry or set up their own companies. What is disturbing about this development is its scale. “It is already apparently true that there is no notable biologist in this field anywhere in America who is not working in some way for a business. I interviewed some two dozen of the best molecular biologists in the country and found none,” wrote U%.rhington Post reporter Philip Hilts in 1982. The heavy involvement of biologists in commercial applications deprives the public, at least for the moment and maybe longer, of an independent source of advice. Certainly, if the DNA hazards debate were to be replayed, or resumed, biologists who denied the risk would be accused of self-interest and their arguments discounted. Beyond that, the widespread commercial interests of all leading practitioners cannot fail-despite their individual denials- to have some impact on the overall direction of research, probably shifting it toward practical goals at the expense of knowledge for its own sake. Engineers, of course, see nothing wrong with that; in their discipline many advances have come from tackling applied problems. But biology is not necessarily the same. Not only may the direction of research be shifted, but also the tradition. Harriet Zuckerman’s study of Nobel Prize winners brings to light how many Nobel-
Biotecbnoiogy and Its Public
21
ists received their training at the hands of other Nobelists. What kind of research tradition will be inculcated into today’s crop of graduate students by professors who arc all engaged in pursuing money as well as truth? Perhaps the present high degree of commercialization of academic biology is merely a temporary phase. Perhaps the applied side of molecular biology will bccome sufficiently divorced from pure research that the same individuals will not be in such heavy demand for both activities. More likely, biologists, having once tasted riches, will not retreat to the cloister or resume their vows of poverty. A Third Phase of Debate What will that do to their public image? After hazards and commercialization, a third phase of debate has just begun, that of the ethics of biotechnology. Biologists have not so far established particularly striking credentials in this arena. The first attempt to apply genetic therapy to humans was undertaken by Martin Clint of the University of California, Los Angeles, who inserted human globin genes into the marrow cells of patients suffering from beta-thalasscmia. There was a touch of envy in the criticisms of some of Clint’s colleagues that the experiment was premature; it was in some ways a bold initiative that, in different circumstances, might have drawn praise. Unfortunately, Cline failed to inform fully some five oversight committees as to his intention of performing the cxpcrimcnt. No other genetic therapists have jumped the gun so far, but the ethics of genetic therapy started off on the wrong foot. More serious than this mishap, however, has been an apparent decision by lcading biologists not to participate in the public debate about human genetic engineering, presumably for fear of stirring up an imbroglio similar to that which surrounded the issue of hazard. This tactical decision makes a great deal of sense if, having learned nothing from the past, one believes that an ignorant public is safer than one in a position to give its informed consent. Its direct consequence is a climate of opinion in which the entire spectrum of church leadership can sign the statement discussed above that calls for a ban on making any inheritable changes to the human gcnomc.
What is the outlook for the future? It is obvious that the more powerful biology becomes, the more its uses and the control of those uses will be debated. If biologists arc perceived to be using their science for their own ends or abusing public trust, they will inevitably lose part or 211of their autonomy. How much better for everyone if biology were to remain a community of autonomous, independent researchers, untrammcllcd by cxccssivc commercial tics, free to give objective advice to whoever wants it, and interested only in the disinterested pursuit of truth. That’s not the way things arc headed at present, but the admirable sense with which biologists have conducted their affairs hitherto will doubtless prevail in the end.