Breaking the Code
As the science and business of genomics become a part of our everyday lives, a range of ethical, social, and political questions must be considered.
 

 
By Mike Fortun

Mike Fortun, Rensselaer assistant professor of science and technology studies, has been at the forefront of the genomics debate in Iceland, where controversy swirls around deCODE Genetics, a company licensed to create the nation’s healthcare database.

Last year, he was awarded a fellowship to spend the 2000-2001 academic year at the Institute for Advanced Study (IAS), in Princeton, N.J., exploring the ethical, legal, and social challenges presented by the Information Age. He will use the year at the IAS to author a book, Promising Genomics, based on dozens of interviews he collected on trips to Iceland.

The IAS was founded in 1930 as a community of postdoctoral scholars where intellectual inquiry could be carried out. Scholars such as Albert Einstein and Freeman Dyson are alumni.

As an anthropologist and historian of science, I have been studying the science, business, ethics, and politics of genomics for more than 10 years. Since 1989, when I started research for my Ph.D. thesis—a history of the scientific developments and policy initiatives that led to the development of the Human Genome Project in the U.S.—I’ve tried to document and analyze the rapid, enormous changes that genomics has undergone.

The scientific and technological progress made in the last decade has been extraordinary: entire genomes of multiple organisms sequenced; increasingly sophisticated bioinformatics tools that allow researchers to combine genetic data with analysis of gene expression in specific tissues, with protein data, with studies of biochemical pathways; and a better understanding of organisms as “complex systems” that are becoming increasingly difficult to describe in the language of genetic determinism, in which genes were supposed to be the “blueprint” or “master program” of an organism.

I would love to devote all my interviews with scientists and all my fieldwork time in labs and at scientific conferences to researching the great scientific achievements of genomics. But genomics is more than a science now—it’s a big business, too. And as the science and business of genomics more and more becomes a part of our everyday lives, it can’t help but produce a range of ethical, social, and political questions and dilemmas. These ethical and social issues are every bit as complex and difficult as the science of genomics itself, and demand the same kinds of concentrated research, theorizing, and experimentation that has worked so well within genomics.

The case of deCODE Genetics in Iceland, which I’ve studied since 1998, exemplifies many of the ethical and social concerns raised by genomics as both science and business. The case shows the powerful connections between information technology and biotechnology, and their social and ethical implications, that are an important part of my research and teaching at Rensselaer.

Founded in 1996 with $12 million in venture capital, and bolstered in February 1998 when the multinational pharmaceutical company Hoffman-LaRoche promised up to $200 million over the following five years, deCODE Genetics in Iceland has been enmeshed in controversy ever since—not only in Iceland, but in the international communities of medicine, genetics, the social sciences, and the media. While some of the issues raised by deCODE’s operation are specific to Iceland as a nation and culture, many of them—questions of informed consent in genetic research, the privacy of medical records, ownership of and access to biosamples, and the future uses of genetic information—are issues of global concern.

(You can already get a sense of how deCODE exemplifies the globalization of genomics as science and business. DeCODE is legally incorporated in Delaware as a U.S. company, and operates in Iceland as Õslensk erfoagreining; Hoffman-LaRoche, formally a Swiss company but with operations around the world, has provided nearly all of deCODE’s operating funds since 1998; deCODE stock is now traded on NASDAQ.)

Why has deCODE raised so many controversies? The concerns center around three different databases that deCODE is trying to build, which are often conflated in many of the media accounts that have covered the story. DeCODE is constructing three databases that will operate separately as well as in combination: 1) a genealogical database of the Icelandic population for most of the last millennium; 2) a genetic database of DNA sequence and other information produced from blood samples currently being collected by deCODE in collaboration with a few physicians and medical organizations; and 3) a database containing past, present, and future medical records from every Icelander, living or dead, produced from the nationalized system of health care, and usually referred to as the Health Sector Database (HSD). The Icelandic government has granted deCode an exclusive 12-year license for the HSD, and it is this database that has drawn the most criticism.

The passage of the HSD Act in the Icelandic Parliament, the Althingi, was contentious and divisive in the scientific and medical communities. DeCODE itself drafted the original legislation and got the Ministry of Health to introduce it in the Althingi in the spring of 1998, hoping for immediate passage with minimal democratic debate. No one in the larger communities of genetics researchers, physicians, and other biomedical professions had been consulted, but a number of them were successful in stopping what most people later agreed was a badly written piece of legislation. Some of their concerns and criticisms resulted in improvements to the original bill over the next eight months, but with the help of powerful allies in the Independence Party (the conservative party which currently holds a majority of seats), deCODE got almost everything it wanted when the Act on a Health Sector Database was finally passed in December 1998.

In the limited space here I can present only a brief summary of only a few of the ethical and social concerns raised by the HSD Act and deCODE’s operations. These fall under the headings of consent, privacy, and finally, an ethics of economic and scientific diversity.

Consent

The Health Sector Database is to be constructed on a principle of “presumed consent” rather than informed consent. That is, rather than informing the citizens of Iceland about the database project, its goals, its risks, and its possible benefits, and then having each citizen give or withhold their consent to have their medical records included in the new database, this common ethical principle of informed consent was stood on its head: by national law, the medical records of every Icelander living or dead were included as part of the database population, with their “presumed consent,” and those still alive are then given an opportunity to fill out a form and “opt out” of the database. If an Icelander changes his or her mind and decides to opt out later, information already entered into the database cannot be withdrawn. Over 19,500 people (out of a population of 280,000) have opted out of the database to date, and the number continues to climb slowly but steadily. (In fact, this computerized list of opt-outs is the only database that exists thus far in Iceland, since the mammoth job of building the HSD itself is still under way. In effect, the database of opt-outs is a kind of database of civil disobedience: an encrypted list of everyone opposed to this piece of government legislation and the private enterprise which it sanctions—with the coding key held by the government’s Director General of Public Health.)

To add to the social, ethical, and legal concerns, the blood samples that are being collected by deCODE and its collaborating physicians to generate DNA sequence and mapping information are being collected on the basis of “open” or “broad consent”— not for a specific research purpose or disease study, as accepted principles of informed consent require, but for any use that deCODE decides to pursue at any time in the future. (And there is at least one documented case, involving a person with multiple sclerosis, where deCODE has repeatedly refused to return the biosample and destroy all data, as this person requested.)

It has to be said that genomics researchers in many countries, including the U.S., are trying to relax the protocols of informed consent in a similar manner, arguing that the risks to research subjects are minimal, and that it’s too burdensome in genomics research, where thousands and even tens of thousands of samples need to be analyzed and compared, to require a researcher to get informed consent from each sample donor for each new biomedical study undertaken. These are difficult and complex issues on which there is much debate, and I won’t pretend to give the “correct” answer here. But Iceland’s relatively small, well-educated, “cooperative,” and geographically concentrated population was one of the assets that deCODE claimed made it unique among genomics companies. I had hoped that those same qualities would also have made it clear that Iceland represented a special opportunity to institute the best possible practices of informed consent for genomics research, where every citizen can be informed about every use to which their DNA is going to be put, and give or withhold their consent each time. But that logic has gone unappreciated.

Privacy

Every Icelander has a national identity card and number, similar to our Social Security number. But their identity numbers appear on everything from their credit cards, drivers licenses, and video rental cards, to their health records. DeCODE often claims that the individual health records that will go into the HSD will be encrypted and anonymized, but things are not nearly so simple. The query structure and other security aspects of the HSD database have been criticized extensively by international database security expert Ross Anderson, and by Oddur Benediktsson ’60, a professor in the computer science department at the University of Iceland. In combination with the other two databases, the Health Sector Database becomes even more concerning. Health records combined with genealogical information, combined with the Icelanders’ often intimate knowledge of their fellow citizens in a small country, makes anonymity and privacy in the HSD even harder to achieve, if not impossible.

Add the genetic database that deCODE is building, and the possibilities become very unpredictable and unsettling. No corporation or nation has ever combined a genealogical database, a database of national medical records, and computerized genetic information at this scale. While Icelanders don’t face the same situation with health insurance companies that so complicates the issues of the privacy of medical records and genetic information here in the U.S., they nevertheless have serious concerns. Recently, the government sought to cut benefit payments to people with a variety of physical and medical disabilities. The Union of Disabled People took their case to the Supreme Court of Iceland, and won their case in January 2001. But with an unprecedented disdain for democratic and legal rule, the Prime Minister continued to withhold the government funds, announcing he would appoint a committee to consider how to “respond” to the Supreme Court decision! Such actions have not inspired confidence among Icelanders that their medical records won’t someday be used against them, through the deCODE-operated database that has making “efficiency” and other cost-cutting recommendations to the government among its explicit goals.

Economic and scientific diversity

The issues of informed consent and privacy are relatively direct. A more indirect set of social and ethical concerns has to do with the threats to what we might call the “research ecology” of Iceland.

DeCODE enjoys extraordinary political power and scientific privilege in Iceland. Its political allies pushed the HSD legislation through the parliament. When Iceland’s National Bioethics Committee was formalizing protocols for informed consent in all biomedical research done there, deCODE complained to the government, and the National Bioethics Committee was summarily dissolved in the summer of 1999 and later reconstituted with different procedures and different members, friendlier to deCODE’s interests. (This scandalous event was well-covered in such scientific journals as Nature Biotechnology. ) And deCODE’s 12-year exclusive license to the HSD presents a number of huge and perhaps insurmountable obstacles to any biomedical researcher not affiliated with deCODE.

Iceland had a diverse and talented biomedical research community—molecular geneticists, population biologists, immunologists, and physicians doing great scientific work at the university, the national hospital, the Cancer Research Society, and other places. They are worried that Icelanders’ trust and willingness to involve themselves in biomedical research may be ruined. Never extravagantly funded to begin with, they now find their research budgets cut even further by a government which can’t understand why all scientific research shouldn’t now be profitable. In my interviews, scientists and physicians who had been doing world-renowned work on the genetics of breast cancer, prostate cancer, schizophrenia, and other conditions, talked about how their research budgets had been cut by the government—or in the case of one hospital, their surgical budget—because of these scientists’ and physicians’ criticism of various aspects of deCODE’s operations.

The new genomics sector in the U.S.—companies like Celera, Human Genome Sciences, and Millennium Pharmaceuticals, and other organizations like The Institute for Genomic Research—owes a good part of its existence and vitality to the high level of public funding that the federal government channeled into genome research in the 1980s and 1990s, at a time when the pharmaceutical industry was not willing to invest in that kind of basic research and technology development. As a result, the U.S. has a relatively diverse genomics “research ecology” of scientists at multiple corporations, universities, nonprofit institutions, and federal laboratories. (This minimizes the serious concerns here in the U.S. about the emerging dominance of one “species,” the corporate researcher, but that is another essay for another day). In Iceland, scientific and economic diversity is seriously threatened, and that diversity is crucial for an enterprise as scientifically complex, medically important, and ethically charged as genomics.

The deCODE case becomes increasingly important as nations like Estonia, Tonga, and the Canadian province of Newfoundland now start to undertake their own population-based, state-sanctioned commercial genomics enterprises. The scientists and politicians involved in these situations often refer to the events in Iceland as lessons in what to avoid: exclusive arrangements, murky political deals, untrustworthy and febrile standards of consent and privacy.

To some extent and with some differences, genomics raises similar concerns for those of us in the U.S., too. As DNA sequencing and genetic analysis become more prevalent and more profitable, and as genetic and health databases increase in size and degree of interconnection, we’re all faced with social and ethical decisions regarding access to our bodies and the information that can be mined from them; the conditions under which our biomaterials and our bioinformation should be stored, shared, sold, used, or destroyed by commercial and/or government organizations; and the degree of respect and involvement to be afforded to people as “research subjects,” necessary for producing new knowledge and a better biomedicine. Sadly, deCODE Genetics may serve the world as the best example of how not to handle such decisions.

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