Unnoticed by the general public, genetic research is changing direction. While the old genome research used relatively rare diseases to understand genetic processes, new research sets out first to understand then to cure the most common diseases. As part of this new research, genetic databases are established, collecting data from large population pools. The potential benefits will be huge, for science, for mankind, certainly for gene-based business. But what of the cost? Should companies be able to hold patents over the building blocks of life? Should society allow the privatisation of genes?
The fiftieth anniversary of the discovery of DNA, the magical helix of life, on 26 February this year, coincides with another anniversary; the first attempt, by the company deCODE, with the help of a parliamentary bill, to set up a comprehensive medical records database, licensed to it in March 1998. The story of the deCODE project raises critical questions about the ethics of gene-business, the processes by which individuals are persuaded to offer their own blood and tissue samples to private companies searching for genes, and the long-term consequences of such projects. Five years on, it is time to reflect on these lessons.
There are few better fitted to tell this tale than Skúli Sigurdsson, from Mannvernd, the Association of Icelanders for Ethics in Science and Medicine, which has led the campaign against the medical records database legislation and the company deCODEs twelve-year license. His is a partisan account, to be sure, written from the inside of the campaign. It is a fastidious and unrelenting chronicle of the painful lessons that have emerged from that long struggle. It contains lessons for all who are concerned with balancing the possibility of eradicating many common diseases, with preventing the privatisation and economic exploitation of the human species.
We look forward to publishing responses from across the spectrum [click here to add your voice]. But taken together, these lessons make an important contribution to a scientific-political argument that is only just beginning to reach the wider audience it deserves.
It is five years since the Icelandic government introduced a law enabling the US/Icelandic private company, deCODE genetics Inc., to pool the medical records of all Icelanders into one Icelandic Health Sector Database (HSD). I would like to offer an overview of the resulting well-known controversy, which has begun to assume something approaching benchmark status. (See for example, Population Databases Boom, From Iceland to the U.S., Science, 8 November 2002.) And I would like to share with you five of the lessons which we learnt - about truth-telling, and the integrity of the political establishment and civil service, together with its commercial and scientific partners, about the importance of our civic culture and democratic processes, and about the need to protect especially vulnerable members of the community.
I had heard about deCODE and Dr Kári Stefánsson, CEO of deCODE in early 1998, but I paid scant attention to the rise of the company. A statement by Dr Stefánsson in a newspaper interview at the beginning of April 1998, however, caught my attention. All diseases which I know of in our society are either totally genetic or have genetic components. Why did the idea of a Health Sector Database have to be sold to the Icelandic public in such banal terms, I found myself asking.
It is worth keeping in mind that rather than some helical zipper at the point of being torn away from its rightful owner or yielding up its malign secrets, genes are still probably nothing more than natures bounty to most Icelanders. Questions over genetic privacy and the ownership of genetic material are rather alien to most of its citizens, currently more concerned with a structural crisis in the National Health Service, the cost of drugs, and the gradual commercialisation of the medical services.
Meanwhile, a commitment to speaking responsibly and intelligibly about technoscience continues to fuel my struggle. In the process, I have joined forces with numerous concerned citizens and experts against the steamrollering of the Health Sector Database and its related legislation through the Icelandic parliamentary system, together with the tailoring of the biomedical regulatory system to serve the interests of deCODE.
Today, some 20,000 Icelandic citizens (out of some 288,000) have chosen to opt out of the proposed HSD, genomics has lost much of its lustre, the new economy has imploded, and the stock market has hit the doldrums. As is often the case in technoscientificpolitical controversies, there is neither closure nor are there clear winners in sight, but a multitude of casualties and losers.
This struggle, against the combined and often inseparable forces of the government and deCODE, has cemented many friendships, taught me much about the functioning of modern democracy, law and media, as well as the limits of idealistic group activism against the powers that be. In my writing you might detect a shift from the combative mode to a more sombre structural analysis of Icelandic society. But you could also say that I, who for the last twenty-five years have lived mainly abroad, am asking myself why, and at what cost, the ideals of my parents generation, namely honesty, integrity, courtesy, and responsibility, have been sacrificed. To answer that question is admittedly a much more difficult task.
Taking stock of this controversy, it may be instructive at the outset to take a look at the website of deCODE (incorporated in the state of Delaware, in 1996). The firms position statement, entitled The deCODE Population Approach, offers the following on the company mission:
The primary focus of deCODEs business is to identify the genetic causes of common diseases and to apply this information to develop new drugs and DNA based diagnostics. Built upon an understanding of the basic biology of human disease, these products are aimed at diagnosing and counteracting the underlying biological mechanisms of disease, not just the signs and symptoms.
Moreover, deCODEs most vital resource is identified the population of Iceland (288, 201 inhabitants on 1 December 2002): A population with all three sets of data genetic, disease and genealogical is the scarce resource in human genetics. In Iceland, deCODE has brought this information together, enabling the company to conduct effective genome- and population-wide linkage scans for disease-linked genes. Using its unique genealogy database, deCODE clusters patients from across the country affected by any disease into large extended families. Applying its high-throughput genotyping capabilities and proprietary datamining products, deCODE can identify small genetic regions shared by related patients.
It is easy to be taken in by deCODEs claim to a special relationship with the Icelandic population, when a good measure of the strength of these ties seems evident in the high participation rate in deCODEs research projects. The company has acquired to date: DNA samples and detailed disease data from approximately 80,000 volunteer participants in more than 50 disease projects. Approximately one-third of the adult population in Iceland is participating in one or more of deCODEs research projects [actually roughly 28%; Sigurdsson], as are more than 90% of Icelanders over the age of 65.
Interestingly, Icelands Health Sector Database (IHD) is, however, no longer central to the corporate vision of deCODE. On the HSD (or IHD as deCODE calls it) the position paper states, as a kind of afterthought: deCODE holds a license from the government of Iceland to build and commercialise the Icelandic Health Sector Database (IHD). Now under construction, the IHD will assemble anonymized, encrypted data from patient records from Icelands national health service in a secure computer system. The IHD will enable users, including doctors in Icelands national health system, to conduct population analyses of longitudinal healthcare data and trends on, for example, clinical measurements and basic lifestyle information, disease diagnoses, treatments and outcomes. deCODE believes that this system will provide a valuable resource for better understanding the environmental components that, along with genetic factors, lie behind the onset of common diseases.
It is true that deCODE was granted this license in January 2000. One of the selling points of the HSD bill in 1998 was indeed the possibility it seemed to offer for reining in escalating health costs. Claiming that the HSD is under construction, however, stretches the truth.
What we do know is that the Icelandic Data Protection Commission (DPC) and deCODE have not reached an agreement on the adequacy of security measures for the HSD. Moreover, negotiations between deCODE and the National-University Hospital in Reykjavík, the largest hospital in Iceland, leading to the construction of the HSD have been postponed indefinitely according to a letter from Dr Kári Stefánsson, CEO of deCODE, to the Director of the National-University Hospital (14 October 2002). As the hospital serves more than half of the population, this postponement effectively signals the end of the HSD project in its current form.
Yet none of these recent developments are mentioned in the news section of the deCODE website, despite the fact that most of the genetic lodestone bubble of 1998, together with the initial investment in the company stock, was largely based on the speculative promise of the HSD.
So truth is the first casualty in the HSD deCODE story.
The second casualty
In the immediate aftermath of the parliamentary passage of the HSD bill in December 1998, Icelandic governmental officials tried to answer criticism of the HSD legislation by presenting a manicured picture of the machinations and public agitation which had accompanied the HSD debate in 1998.
In a letter to Science in late January 1999, Ms Ragnheidur Haraldsdóttir, Deputy Permanent Secretary of Icelands Ministry of Health and Social Security, wrote: The [HSD] bill has been harshly criticised, but it has also received substantial praise for its progressive stance and its promise to preserve human rights while facilitating scientific endeavours for the benefit of health.
Ms Haraldsdóttir was correct in observing that the HSD legislation had been subjected to harsh criticism, domestically and internationally. The claim that it had been praised was a mixture of wishful thinking, total absorption of the deCODE corporate vision, and wilful or woeful ignorance of the politics involved in the passage of the HSD bill. Ms Haraldsdóttir continued: Iceland has outstanding health statistics, a high quality of health care, thorough patient and genealogy records, and a well-educated public in favour of participating in an experience such as the one proposed in the bill. This situation imposes on us an ethical obligation and gives us a unique opportunity to promote medical sciences.
It only remained for Dr Stefánsson, in dismissing the critics of deCODE and the HSD legislation, to make the non-governmental organisation Mannvernd the Association of Icelanders for Ethics in Science and Medicine (established in October 1998) the target of his most sustained attacks. Interviewed on the HSD in New Scientist (July 2000) he dismissed Mannvernd as a completely inconsequential organisation and claimed that deCODE was in tune with the moral majority. Dr Stefánsson asserted that 90% of the population was in favour of the HSD project (a more accurate number according to a Gallup survey conducted in the spring of 2000, sponsored by deCODE, would have been 81% in favour, 9% undecided and 10% opposed).
Ethics compelled assent. They had the effect of silencing critics as if they were slightly perverse, instead of engaging in a critical open dialogue (see www.gene-watch.org). After all, who would not want to help little Johnny-next-door receive treatment for a mysterious disease, and promote health worldwide to boot? In retrospect, this appeal to an ethical obligation depended for its effectiveness on a weak civic culture. A more sophisticated grasp of the issues would soon have registered the disproportionate nature of the claim that such a small society was able to contribute significantly to the betterment of world health, as if the Icelanders were some kind of genetically chosen people.
The position adopted, for example, by Ms Haraldsdóttir, points us to the second casualty of the controversy: the integrity of the political establishment and the civil service.
Promises and progress: a third lesson
Events in Iceland since 1998 demonstrate the high risk of combining promises and medical progress. The stock market is forward looking. It is about future scenarios, hedging your bets, and forward-looking statements according to the US Securities and Exchange Commission parlance. A news release on deCODEs website (as of 20 November 2002) concerning a collaboration between deCODE and Wyeth in pharmacogenomics spells out the standard disclaimer:Any statements contained in this presentation that relate to future plans, events or performance are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to a number of risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. These risks and uncertainties include, among others, those relating to technology and product development, integration of acquired businesses, market acceptance, government regulation and regulatory approval processes, intellectual property rights and litigation, dependence on collaborative relationships, ability to obtain financing, competitive products, industry trends and other risks identified in deCODEs filings with the Securities and Exchange Commission. deCODE undertakes no obligation to update or alter these forward-looking statements as a result of new information, future events or otherwise.
Though shrouded in SEC legalese, the implication is clear. The future is open and uncertain, and, as we see from the last sentence, deCODE is under no obligation to act as its own historian. Neither, we must conclude, is the company therefore obliged to inform website visitors of the fact that the HSD is now a mirage.
The fine print of the US Private Securities Litigation Reform Act of 1995 diminishes, but does not eliminate, punitive measures for promises that are blatantly deceptive or false (i.e. by extending the reach of the safe harbour principle), but the same is not the case in biomedicine and history.
The French molecular biologist François Jacob once remarked that experimental systems are machines for making the future. Science is fundamentally about forward-looking statements, the making of utopias, and jumping into the unknown. In traditional parlance, the reward for this daring is called progress. Can one be against progress? Can one be against scientific visions, promises or rallying cries (which may turn out to be false)? Can one be against helping patients who suffer from multiple sclerosis or mysterious genetic afflictions? Isnt progress-bashing always an irresponsible kind of cynicism, a kind of perversion?
You will not find the perversion argument voiced publicly in support of the HSD legislation. Yet in private conversations, it soon became clear to critics of the HSD bill, the government and deCODE, that this was the basic assumption of the average citizen. Critics who had no children were told by the average conformist citizen in no uncertain terms that they were disqualified from discussing the HSD. Yet, the very same exemplary citizens seem to have overlooked, together with the Icelandic ombudsman for children, the fact that neither children nor the dead could opt out of the HSD.
Now that the promises of deCODE have turned sour and the HSD turned out to be a Fata Morgana, silence has fallen on the population. The welfare-of-children advocates have done little to address their earlier slights. It is probably difficult for most of them and other deCODE enthusiasts to accept the fact that they were manipulated in the halcyon days of the late 1990s, that they fell for an equation of economic promise and medical progress, and contributed unwittingly to the erosion of civic culture and human rights in Iceland a further casualty.
With the intensity of the debate in 1998 still fresh in public memory, a favourite strategy of those sympathetic to the HSD legislation was to emphasise that it was the result of a democratic process. Like the appeal to ethical obligations by Icelandic civil servants, this containment strategy underestimated the momentum that the controversy had gained, domestically and internationally.
Critics such as Mannvernd and the Icelandic Medical Association (IMA) did not question the fact that the HSD bill had been passed by a democratically elected assembly. But they insisted that the law violated internationally sanctioned norms of biomedical practice (i.e. presumed instead of informed consent), disturbed the doctorpatient relationship and encroached upon the freedom of science (the HSD would give deCODE a monopoly control of health records).
Critics began with the feeling that the law was unacceptable. Further acquaintance with the operations of deCODE, its close ties to the Icelandic government, and various attempts to silence them, have only fuelled the moral indignation which informs this fight.
In late winter and spring of 1999, Mannvernd was at the centre of the controversy, while concerned health professionals were encouraging citizens to opt out of the HSD. deCODE, on the other hand, appealed to citizens responsibility to contribute to the global improvement of health and help fight diseases by agreeing to stay in the HSD (this meant that they had to do nothing).
This battle for the minds of the citizenry was novel territory for all parties concerned. Acts of civil disobedience are rare in Iceland, and trust in the National Health Service is high. Nevertheless, by late June 1999 more than 10,000 citizens had chosen to opt out of the HSD. Although the exponential opt-out rate of spring 1999 has not been matched since, the number of opt outs grew rapidly until the late summer of 2000 and has risen slowly ever since (20,381 opt-outs as of 2 December 2002). After the battle for minds came to a momentary standstill in the summer of 1999, we must presume that the continuing opt-outs were mainly a reaction to news suggesting confirmation of the HSD becoming a reality: the granting of the HSD license in January 2000; deCODE filing an application with the Securities and Exchange Commission in Washington DC in March 2000 prior to its Initial Public Offering (IPO); and the IPO on NASDAQ in July 2000. Subsequent slackening of the opt-out rate is probably a fair measure of how much the HSD has receded simultaneously out of the public mind and the deCODE corporate consciousness.
In an interview on a website run by the Elsevier publishing house in January 1999, Dr Stefánsson, discussing the HSD legislation, said: We have basically set a standard of decision-making. As a result, 75 percent of our people support it. Besides trying to legitimate a controversial parliamentary decision, the aim of this claim was to marginalize and silence the critics. He added: The critics are a minority. And if they persist, they not only criticise the [HSD] project, but the functioning of democracy itself. In time, it came to seem as if this issue of whether or not the HSD would ever actually be constructed, mattered far less than the show of community support which it made possible.
In a comment in Nature Biotechnology in July 1999, Dr Jeffrey R. Gulcher of deCODE and Dr Stefánsson wrote: One of the conditions that the international bioethics community sets for research on populations is consent from the communities. It is, however, not easy to find definitions of what community consent is. We believe the way in which Icelanders handled the database idea provides a reasonable definition of the concept of community consent.
Few observers of the local Icelandic political scene would agree with this. Yet, the argument was frequently used by deCODE and its fellow travellers outside and inside Iceland. In an interview on the Icelandic State Television in the summer of 1999, the anthropologist Paul Rabinow, referring to the HSD debate with the logo of deCODE in the background, said: So, I think that what I am saying in two words is that the process has been democratic and passionate. I think it is time to move on to the next set of debates, both in Iceland and outside Iceland to make sure that this is done well so other countries can follow a model of what Iceland has done.
Escalating opt-outs were a serious cause for concern for deCODE prior to the IPO on NASDAQ, not so much because they threatened the viability of the HSD project, but rather because this reaction would seem to tarnish the image of deCODE enjoying an especially close and amicable relationship with the Icelandic population. deCODEs current position statement shows what a key corporate asset the idea of a whole committed nation remains a rhetorical ploy abetted by the special status which islands enjoy in evolutionary theory.
Opinion poll results were needed to help construct a corporate image for deCODE that made it out to be synonymous with Iceland when it came to advanced biomedical research. In 1999, in a letter to Nature Gulcher and Stefánsson wrote: On the eve of the vote on the [HSD] bill, a poll showed that 75% of the population supported it, and Althingi passed it last December by the same margin. By correlating the results of an opinion poll and the vote cast in Althingi, the Icelandic parliament, deCODE were trying to argue that the parliamentary decision expressed the will of the nation in a one-to-one fashion.
Finally, how is one to interpret the striking fact, according to deCODEs current position statement, that out of the 80,000 Icelandic volunteers taking part in numerous deCODE research projects, the participation rate of over-65s is huge: 90%?
A key must be found in the neo-liberal political culture of the late twentieth century, the common context uniting such disparate actors as Dr Stefánsson of deCODE, and Tom Miller of the Cato Institute. They emphasise freedom, envisage a future of interventionist or preventative medicine, question the abuse-model of knowledge, celebrate the market, and value weak regulatory regimes. Theirs is a world of intelligent social players making informed choices.
In an interview in EMBO Reports in the fall of 2001, Dr Stefánsson was quoted as saying: I think that the more knowledge we have, the more opportunity we have to make intelligent choices, and the better society will be. I am absolutely convinced of that. The ideal intelligent social player needs neither protection nor advice. Dr Stefánsson in the same interview said: Ethics was a scholarly discipline, but now we have people from universities telling other people what they should do, which I think is dangerous. That is something that society has to do.
It is easy to see what this atomised societal vision entails. It takes advantage of vulnerable populations, such as the elderly in Iceland. They go to their physicians, many of whom are collaborating with deCODE at the local level, and sign informed-consent forms. What would an intelligent choice be in their case?
Neither deCODE nor the IMA has done much publicly to inform the elderly of their rights, and what it means to become a biomedical research subject. In the fall of 1998, Dr Stefánsson clarified what he considers of paramount importance in this regard. In an article in Nature Biotechnology conceding that the notion of presumed consent was not the one adopted by the American Society of Human Genetics, he countered with his belief that patients do not need to understand the fine detail of every genetics study to which their data or biological samples might contribute. It would suffice that they understand their own desire to contribute to the advancement of science: As a patient, my right of self-determination is a fundamental right. [By contrast], the view of what is informed consent is constantly changing.
It is clear that Icelandic patients believed the promises made in the name of progress and the advancement of science. One wishes that they had been properly empowered to make intelligent choices. Patients need to understand their own desires, so that they can exercise their fundamental right of self-determination. Instead of being exploited, shouldnt the old and vulnerable be treated with respect?
Thanks to the Max Planck Institute for the History of Science in Berlin, Germany for its hospitality, and for helpful discussions, encouragement and assistance from Rosemary Bechler, Bogi Andersen, Davíd Kristinsson, Raphael Falk, Mike Fortun, Eric Francoeur, Gudsteinn Bjarnason, Jón Ólafsson, Renato Mazzolini, Michael Rebehn, Simon Schaffer, Elvira Scheich, and Ingrid Schneider.
In the halcyon days of the late 1990s, when the Human Genome Initiative and the dot.com boom seemed to open up boundless economic vistas, the Icelandic population became the object of energetic promotional activity on the part of deCODE. They were, it was claimed, genetically pure, genealogically descendent from Viking forebears, and in possession of sterling health records from 1915 onwards.
This genetic lodestone attracted numerous scientists, foreign venture capital (primarily from the United States), a much-touted $200 million dollar deal with a Swiss pharmaceutical giant, hundreds of jobs, high salaries, and an $182 million dollar initial public offering (IPO) on NASDAQ, not to mention foreign journalists, radio and television crews, film makers, social scientists, and bioethicists all thronging to Iceland.
February 1998 When the news broke in Iceland about the deal struck between deCODE and the Swiss pharmaceutical giant HoffmannLa Roche concerning research on twelve common diseases, the only language available to this society with such a thin tradition of biomedical research and biopolitical discourse, seemed to be that of fisheries. At the time, the largest Icelandic newspaper Morgunbladid and a staunch supporter of deCODE described the deal between deCODE and Roche in ecstatic terms, predicting a trawl of $200 million for a period of five years. It quoted the Icelandic Prime Minister, Mr. Davíd Oddsson, saying that the deal equalled in value the catch from a good season of capelin. The advantage this agreement had, in comparison to those of large industries, was that it caused little or no pollution.
What was not known at the time was that the deCODERoche agreement was not for five years, but for three, with the possibility of two one-year extensions. Nor was the $200 million a guaranteed catch. The agreement promised $70 million for research costs. The remaining $130 million would only be paid if certain research milestones (such as identifying genes) were reached by deCODE.
March 1998 Barely two months later just before Easter, when the first HSD bill was introduced (a draft having been faxed by deCODE to the Ministry of Health and Social Security in September 1997) the conditional nature of the deCODERoche agreement had metamorphosed into a fixed certainty. It was as if the unique nature of Icelands genetic endowment would itself guarantee that all the milestones would be realised. However, the strategy of letting the $200 million dollar super deal speed through approval of the HSD bill did not work.
December 1998 It was only nine months later just before Christmas that the HSD bill was passed.
1999 and 2000 deCODE stock traded on the grey market in Iceland for prices in the range of $30 to $65 a share, this speculative frenzy was in part fuelled by regular deCODE news releases of genetic discoveries, unaccompanied by any data or other material that would have enabled people to make an informed decision.
July 2000 Initial Public Offering on NASDAQ. deCODE stocks are launched at $18 and peak at $28.70 shortly afterwards.
Spring 2002 The $200 million story acquired such momentum that it was not until four years later that the true nature of the deCODE-Roche deal was fully understood in Iceland. As deCODEs later filings with the US Securities and Exchange Commission (SEC) made clear, the February 1998 deCODERoche connection had actually yielded only $74.3 million. Of that, only $18.3 was for research milestones or scientific achievements; the rest ($56 million) for operation costs. It had been extended once through January 2002 (although the collaboration between deCODE and Roche is now under a new agreement).
April 2002 The terms of the 1998 agreement came to be scrutinised, with deCODE stock rapidly declining in value and the company having high operating costs (around 600 people on the payroll), but little to offer in terms of concrete results. On a second occasion the Icelandic people were asked for their support (having already bought deCODE stock). The result was a parliamentary bill introduced just after Easter, authorising the Minister of Finance to extend a loan guarantee of up to $200 million to deCODE. This met with considerable parliamentary opposition and general public disapproval, but again the solid majority of Mr. Oddssons coalition government ensured its passage (the authorisation has still to be implemented).
14 November 2002 A Gallup survey of the investment landscape in Iceland shows that investors have absolutely no interest in buying deCODE stock which trades at a meagre $2 to $3 a share.
The capelin that got away The loan guarantee debate of the spring of 2002, the continued free fall of deCODE stock, the mirage-like nature of the HSD, the fact that public health costs continue to spiral, the fact that a good part of the IPO investment came from Icelandic sources, the string of personal bankruptcies, and the fact that 200 deCODE employees were laid off in September 2002 - these are the true milestones in the gradual unravelling of the status which deCODE has enjoyed in Iceland.
The story of the meteoric rise and ruinous free fall of deCODE stock has been fully recounted by James Meek in a feature article in The Guardian (31 October, 2002) and by Jill Lawless (Associated Press) in The Washington Times (2 December, 2002).
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