From the conference Biotechnology and Ethics: A Blueprint For The Future

Biotechnology: Social Impact and Quandaries

Vivian Weil
Director, Center for the Study of Ethics in the Professions
Illinois Institute of Technology

I will make the transition from talking about biotechnology to talking about ethics. An example from a newspaper report will illustrate how ethical issues show up. There was a story that hit the front page of the business section of the New York Times early this month about a race to develop a new product in biotechnology. The title is "Down on the Farm, A Donor: Genetically Altered Pigs Bred for Organ Transplants."

Four small biotechnology companies are competing to develop pigs as sources of organs for humans. The recent progress made by the companies and their academic collaborators prompted some of the scientists to announce that the first organ transplant from a pig to a human could occur within a year. They say that xenotransplants (a term coined for cross-species transplants) could become commonplace a decade from now.

Of course, significant medical and technical hurdles are still to be overcome, but the under-supply of human organs for so-called "qualified" patients presents a powerful motivation for investing in the race. Major pharmaceutical and medical device companies, such as Sandoz Ltd., Baxter Health Care, Inc., and the U.S. Surgical Corporation have already made significant investments in the four small companies, and others are looking for a way to jump in.

The description of the breeding process emphasizes the use of "sterile sties" that are alleged to be comparable to the "clean rooms" of the computer software industry. The companies see the sale of organs to hospitals as complementing their existing business in immune suppressant drugs, blood products, and surgical instruments for transplant operations. They foresee business on a scale of over $1 billion in annual sales, admittedly a projection at least five years into the future. Nevertheless, some analysts predict an average selling price of $10,000 for pig organs.

In the continuation of the story occupying most of an inside page of the business section, the reporter notes the concern of some scientists about this development. An opinion piece in a recent issue of the New England Journal of Medicine advocated stricter review of these advances, calling attention to the potential for cross-species disease transmission. Proponents of xenotransplants voice confidence that this issue can be dealt with, citing the alarms that were raised by the first human-to-human transplants. They are nevertheless proceeding quietly, worried that interest groups opposed to the genetic modification of living creatures may generate controversies that will impede progress.

This story brings into focus the tangle of issues that precipitates quandaries about biotechnology development. A dramatic technical "breakthrough" suddenly receives front-page attention, often on the business page. It is the commercial aspect that commands attention. Just as abruptly, the spotlight turns away; there is little or no follow-up. Ongoing activities remain out of view. As we learn here, those involved in new developments may prefer to proceed quietly so as not to stir up controversy.

After noting the anticipated medical benefits, the story concentrates on the expected business profits and only afterward mentions some critical concerns. Words of caution from scientists, coming toward the end, are not fully developed, and ethical concerns are not mentioned as such. Proponents worry that "animal rights or religious groups opposed to the genetic manipulation of living creatures may raise emotional and political barriers to progress. In this story, as in many others, commercial interest frames an account which suggests a too-simple polarity between two broad groups: proponents advocating continued advancing developing and producing biotechnology and opponents stressing caution, limits, and control.

From an ethical perspective, biotechnology is an especially challenging domain to examine for at least three reasons. One is the point just made about the kind of visibility given to biotechnology. A flurry of publicity attaches to a controversial new development such as the introduction of the bovine growth hormone in 1994, with little follow-up. Uncontroversial successes such as recombinant insulin get little attention. Those on the inside of developments in universities and companies, as well as those on the outside, often lack information and occasions for fully considering the complexity of the issues surrounding these enterprises.

A second reason that this is an especially challenging world is the great and expanding range of areas of research and development with commercial potential and implementation. Advances in genetic modification using recombinant DNA technology occur at many fronts, including the manipulation of viruses, bacteria, plants, animals, fish, and birds. These enterprises have important impacts in agriculture, in the manufacture of chemicals and pharmaceuticals, in medicine, and in the use of animals for medical research and therapy. The mapping of the human genome, itself a large enterprise, is rapidly providing a flood of information relevant to individuals' critical life choices and with potential for the commercial profit of companies. Quandaries arise from surprising directions. Take the instance of a Maori woman from New Zealand who spoke recently on National Public Radio's "Marketplace," discussing the patenting of Maori genes. She said that Maori do not mind the advance of scientific understanding but they object to the companies making profits with no benefits to the Maori.

The third reason that this domain is so challenging is there is also a considerable range of ethical concern and they surface in a great tangle, intertwined with scientific, philosophical, economic, and political issues. In the mix are threats to the world views people have, including views about the treatment of humans and animals, in some cases religiously-based; slippery slope risks — some empirically based and others a matter of logic; socio-economic risks, such as the elimination of small and moderate size farms, also amenable to scientific investigation, but not by biologists; risks to universities from collaboration with private companies, topic that has been studied for over a decade; and concerns about risks to health and the environment that are amenable to scientific investigation by biological scientists, not only molecular biologists;

I will take it as my task to sort out impacts and quandaries and indicate how they might be addressed. In my survey of ways to respond to the quandaries, I will emphasize the role that research from different disciplines can play and point to ethical responsibilities of scientists and other technical professionals.

One helpful way to approach ethical quandaries is by categorizing risks. I have categorized and ordered risks to help academic and company technical people in biotechnology disentangle knotted issues and see how to reflect about their own professional responsibilities. First, I will consider risks to world-views and the closely related "slippery slope risks." Second will come consideration of social and economic impacts. Finally, I will concentrate on risks to animal and human health and to the environment.

We have to give proper regard to the religiously or philosophically-based fears that the new enterprises of genetic modification may undermine our conceptions of ourselves and other living species. The general imperative to respect other persons requires it. The fears do not seem far-fetched when we consider that both supporters and critics of molecular genetics agree on the magnitude of the transformation in our thinking that molecular genetics is producing. And it is well to remember that riding roughshod over traditional beliefs or world views integral to people's self-perception can produce powerful resistance.

These fears are often fueled by a concern that such shifts in our thinking may allow tampering with the genetic inheritance of species in an irreversible slide to unchecked commodification of animals and finally to genetic manipulation of humans. Sometimes, instead of the slippery slope, the image of a damn burst is invoked. The idea is that if we begin with "transgenic alteration of inherited materials, the process will be pursued to the point where the human genotype is also altered."

Philosophers and other specialists have had to pay attention to slippery slope arguments in relation to other practices, for example, certain punishments, abortion, and physician-assisted suicide. Bernard Williams, a noted philosopher, has written an interesting article titled, "Which Slopes are Slippery." Some arguments for slippery slopes are based on empirical data or on observations in analogous areas. Sometimes, the argument is a matter of logic: the justification for taking the first step cannot be withheld from each succeeding similar step.

An advantage of separating out this issue is that these arguments can receive appropriate attention. Those who hold the position that tinkering in genetic technology poses the risks of the slippery slope scenarios could concentrate on building arguments to show why these fears are real and substantial. There may be good arguments for the slippery slopes biotechnology may cause. In any event, it may help to lessen controversy if these risks are not confused with others.

In my second category are risks of adverse social and economic impacts from introducing genetically modified plants and animals in agriculture, from the new concentrations of power in large chemical and pharmaceutical companies, and from university/industry relationships.

In agriculture, questions concern effects on rural income levels and distributions of income. Technological advances often bring disproportionate disadvantages to farmers with moderate and small scale farms. This is a consideration of justice, and it applies as well to third world countries.

Of course, the introduction of new technologies always puts some workers out of business. The dislocation produces pains for the displaced and costs to society. However, the costs can be ethically justified when there are social benefits that clearly outweigh the costs and there are remedies for those harmed. It may be possible to prevent future injustices by making use of what we learn from sophisticated economic studies about the effects of various factors on farm size and profitability. The notion of "potential future injustices" suggested by Gary Comstock may help to frame our thinking. As he points out, having the power to prevent an injustice before the fact is surely better than trying to remedy it after the fact. Here technical people in biotechnology may be able to make a contribution by paying attention to requirements for managing a technology they are occupied with. Professional engineers learn to think about such requirements.

What is the concern about the increased concentration of economic power in the large chemical firms, such as DuPont and Monsanto, that invest in, for example, genetically modified virus-resistant and herbicide-resistant crops? The risk is that the increase of their power in the agriculture industry will result in higher prices that farmers have to pay for seeds and chemicals and ultimately in higher prices for consumers. Technical people in biotechnology are not entitled to ignore this issue.

The third concern has to do with a distinctive feature of biotechnology development, collaborations between academic and company researchers. From the beginning, these relationships raised questions, centering on the prospect of harm to universities from too close an association with commerce. Universities are valuable partners in these collaborations because of the kind of institutions they are. It is in everyone's interest to protect the character of universities as institutions for teaching and independent research. This issue has received careful, systematic investigation. That has led to policies and mechanisms for promoting open publication, handling academics' conflict-of-interest problems, and dealing with intellectual property issues. These policies and mechanisms require continuing evaluation by individuals and institutions and a willingness to make changes when experience shows the need.

I turn now to risks to human and animal health and the environment. Many different kinds of developments raise concern about such risks. Different kinds of developments should not be lumped together. And we have the risks of normal operations, risks of breakdowns, and risks of misuse. In genetic technology, many point to the risks of extensive success. To make headway here, we need to acquire the necessary ethical vocabulary and learn the nuances of moral reasoning.

Take for instance the risk that herbicide-resistant crops will become weeds or cross with weedy relatives and spread herbicide-resistance into week species. It will not be an adequate answer to this concern to cite food needs of the world's population in the years ahead and the boost that such crops are projected to give to food production. Feeding the world's hungry is an ethical goal, but it does not automatically trump all other considerations.

Among other considerations raised by this risk is the question of how to deal with scientific disagreements, uncertainties, and unknowns. These are issues for scientists and technical people, though not for them alone. Notice that the risks in question from herbicide-resistant crops concern the release of genetically altered organisms. There is disagreement among scientists about the risks of release, in part because research in this area of biology has not been funded as well as molecular biology; so we lack investigative findings.

There is another feature to the debates among scientists, disagreements in the assessment of risks by molecular biologists on the one hand and ecologists on the other. On scientific grounds, the molecular biologist views the risks as minimal and under control. But the ecologist, also on scientific grounds, is more impressed with the risks, viewing them as deserving careful scrutiny and requiring a cautious approach. One way to understand this disagreement is by seeing the opposing scientists as holding different views about the errors that need to be addressed and the controls that are needed to address them.

The molecular biologist is occupied with errors that can occur in the lab in the process of tinkering to arrive at a desired product. The concern is with things that can go wrong so that the tinkering fails to result in a product with the desired characteristics. In the lab, the molecular biologist seeks knowledge that makes it highly unlikely that some unexpected or uncontrollable sequence would result once the product is used. The molecular biologist reasons that there is a high probability that such a risk, if it exists, would have come to light in considerable lab experience with well-characterized genes.

Ecologists are concerned that control in the lab over the error of getting the wrong product need not insure control over the error of getting unpredicted outcomes in the field. Even extensive experience in the lab, they hold, is not likely to pick up information that will predict how an organism might fare outside the lab "where a multitude of ecological factors are acting and interacting." For ecologists, the concern is with the error of unanticipated consequences that might occur in an actual ecosystem.

For addressing this conflict over risk judgments, we need more research, bringing together people from different disciplines. One aim would be, as Deborah Mayo, has suggested to identify those cases where the lab experience really does rule out the error of unpredicted, unwelcome outcomes outside the lab. Those instances might serve as exemplars. A second aim would be to explain why in other cases lab experience was not adequate to rule out errors in the field. A third would be to identify the modified organisms that pose the highest potential dangers.

Virus Resistant Plants and donor Pigs

An example of some recent research indicates one kind of investigation that may be useful. The example also shows how empirical investigation has to be accompanied by increased sophistication in moral reasoning. In 1994, some investigators at Michigan State University described their findings on some transgenic plants in the Reports Section of Science. In the Perspectives Section, Science ran an accompanying dissenting article. The New York Times provided an account of the research and the criticism.

The scientists inserted pieces of genes from plant viruses to make virus-resistant plants. They found that the inserted genes can recombine with natural plant viruses to produce wholly new viruses at a rate much higher than previously reported, and therefore, a rate higher than had been expected by experts at the Environmental Protection Agency and the Department of Agriculture. The investigators concluded very carefully that "RNA recombination should be considered when analyzing the risks posed by virus-resistant transgenic plants." It seems that genetic modification to produce virus resistance might lead to new, more virulent plant viruses that could damage harvests.

The authors who disputed the research acknowledged that the investigation clearly and elegantly showed a significantly higher rate of recombination in this instance. They pointed out, however, that such recombination occurs in nature (when a plant is infected with more than one virus), but that new viruses arise more often from minor variants of known viruses than from recombination. The critics conceded that traditional plant breeding has fostered the emergence of virulent virus strains, and they could provide only good guesses about genetically engineered plants. They reasoned that just as the costs of those new virulent strains is much less than the cost of abandoning plant breeding, so the potential benefits of engineered virus-resistance outweigh the risk of creating harmful, new viruses greatly in excess over those created by natural processes.

This is not careful cost/benefit analysis and reasoning by analogy but a swift, sweeping conclusion that leaps over the evidence and the modes caution drawn form it. And it closes off an opportunity to reflect on what further research it might be useful to conduct.

Another example will show the need to develop more sophisticated reasoning and carefully constructed procedures for dealing with unknown risks to human health. A few days after the pig donor report, the Science Times section of The New York Times carried a long article about the risks to human health from cross-species transplants. One scientist has "sounded an alarm about the theoretical risk that known or unknown animal viruses may infect human recipients and then be transmitted to other people."

Many others share his concern but have not spoken publicly, to the surprise of Food and Drug Administration officials. Why not? For some it may be timidity about interfering with "progress" or the hesitation to break ranks; or it may be the belief that other countries will proceed and get ahead of the US. Some put their faith in careful monitoring of early recipients. Proposed Federal guidelines are expected to put primary responsibility on the researchers carrying out the xenotransplant, requiring them to get approval from an independent committee yet to be defined. Health officials are looking for guidance from interested groups after the guidelines are published in the Federal Register. One government official said, "The thorniest thing to wrestle with here is how much risk actually exists and how much impedance of progress is justified in protecting against incalculable risk. None of us are absolutely confident that we have the right answer for that." Defining the composition of the independent committee is part of the answer.

What are the responsibilities of professional technical people, in universities or companies, in a highly charged commercial climate and with government agencies trying to figure out how to respond to emerging innovations and risks. Dan Callahan talked about self-imposed limits. Here are suggestions for such limits.

First, technical people, at every level, have to take note of their role in generating innovations that produce the quandaries and impacts to which I have drawn attention. This is part of, not separate from, doing science. And faculty have to alert their students to this dimension of their role as technical people in biotechnology.

Second, people in biotechnology have to reflect about the kind of research they do. The directions that technical professionals in biotechnology chose to pursue in their work lead to products that really do make a difference to many social practices and to the critical life choices of many people. Research is, of course, driven by a number of factors; important among them are the interests and requirements of the public institutions and private corporations that provide the funding. But scientists do not passively respond to client demands; they contribute to the agenda setting process. The direction of research is an outcome of processes of negotiation and persuasion rather than coercion. In the end, scientists have to make their own assessments of the appropriateness and feasibility of a line of research. Moreover, researchers control the supply of research when they are the only ones who fully understand how research can be brought to bear to respond to demands of clients. Scientists, therefore, have some latitude for defining the research. Support might be obtained for research that could produce understanding of risks. The funding for the research on virus-resistant plants came jointly from Monsanto and the Department of Agriculture.

It may be especially difficult for technical professionals in biotechnology to step back and reflect as required. That is because enormous amounts in funding are made available for their efforts and they are aware of strong political encouragement to move forward. Furthermore, it can be intimidating to ask questions about operations of major companies which have moved into this area, with their wealth, power, status, and even ability to articulate their demands. These circumstances add to the difficulty, but also the need, for technical people in companies and out;side to take a critical perspective on the work they choose to do.

Third, they should address benefits and risks more openly. They need to give more candid accounts to decision makes and the public about dangers as well as promises of new biotechnologies. The news report about health risks from xenotransplantation noted the diffidence of scientists, not surprising when we consider that their training may not have prepared them for speaking about their work. Here is an issue of public trust. Instead of sidestepping questions, scientists can clarify what they know and discuss the limits of their knowledge.

Fourth, they have to give more systematic attention to the uncertainties and unknowns. This means not only more resources for research by biologists in other fields to extend the scanty knowledge base for anticipating consequences from large-scale use. It also means new kinds of endeavors such as developing routines for identifying uncertainties, for communicating about them, and for long term monitoring. Public debate that brings in many perspectives should be welcomed. To my knowledge, xenotransplantation, has not been discussed in the context of priorities in health care and containment of health care costs. As we noted with regard to the procedure for generating government guidelines, there is a role for members of the public to play.

Some of the responses I have suggested are available to individuals: individuals can note the role they play in generating knowledge and products that produce quandaries; they can attend to their own choices about projects to pursue; and they can even speak more candidly. Collective efforts through professional societies or networking through BIO are needed to create mechanisms to deal with uncertainties and unknowns, and they can facilitate the other responses.

As we have seen, it is easy and unhelpful to succumb to oversimplification. Much more discussion is needed to bring out the range of considerations essential to making sound judgments. We need sound judgment not just technical expertise. Yet the complexities and unknowns should not make people feel powerless. Paying attention to ethical issues can make it possible not to acquiesce in processes that seem inevitable but are not. As another observer noted, scrutiny of the science in light of moral and social insight is empowering.

Center for Biotechnology, [email protected]
Ph: (847)467-1454, Fax: (847)467-2180
Northwestern University