As the field of genomic research continues to grow, researchers are faced with ethical dilemmas: what to do with all the data that's generated from ever-faster, ever-cheaper sequencing machines, whether to go back and ask for consent again when using samples in a different way from what was originally stated, making sure that — no matter what — study participants are treated in as dignified a manner as possible.
It's hard enough to accomplish all this in places like the US and Europe, where at least some of the public has heard or read about recent scientific advances, knows what a clinical trial is, and is legally protected from ethical slip-ups. It's another thing entirely when researchers work in places that don't offer much legal protection for research participants, or where the population hasn't heard about the latest scientific discoveries.
Important research is being done in developing nations with the goal of improving and saving the lives of native peoples, but in many such countries, scientists are also trying to work out ethical best practices. Though there are still problems that will take years to solve, some researchers have found practical solutions to ethical problems in the field. "I think the ethical issues, in a sense, relate to questions of feasibility in the circumstances, in which you can't always guarantee what the capacity is of researchers, and indeed the healthcare system in the country," says University College London's Albert Weale, who chairs the Nuffield Council on Bioethics. "So it's how to take general ideas of good practice and adapt them to circumstances of the country."
The Malaria Genomic Epidemiology Network was launched in 2005 with the aim of understanding the genetic and genomic reasons behind susceptibility to the disease, and to develop tools to control it. The project brought together researchers from more than 20 countries, doing research at multiple sites across Africa, Asia, and Oceania. Because most of the research sites were located in developing nations, one sub-study of the overall project focused on the ethical implications of doing genome-wide association studies there.
Jantina de Vries, then of the University of Oxford's Ethox Centre, was lead author on the paper that resulted from that effort, published in BMC Medical Ethics in March. There are obvious problems that result from doing research in places like Africa, says de Vries, who is now at the University of Cape Town, in South Africa, and at the top of that list is the issue of informed consent. "How do you even explain something like genomics to someone who hasn't finished secondary education, for instance?" she asks.
Ethox Centre researcher Michael Parker, senior author on the MalariaGEN ethics study, says that many issues seem to arise in the area of consent and comprehension. "If you're doing a big genomics study like this involving collecting data, genotyping and sequencing, and then sharing that data with the community, that's going to raise challenges about how to explain that in a setting where people may not have encountered this kind of work before," he says. But it's not just a matter of getting the science across. "There are all sorts of issues about explanation and understanding — making sure that people understand this is research rather than health care," he says. "When you're dealing with people with very sick children, for example — when you have people that are very distressed — how can you ensure that they are in a position to make a balanced judgment about whether or not they want to be involved?"
Adding to the consent problem is that in some populations, consent must be garnered from the community as a whole and not just from the individual, University College London's Weale says. According to a 2002 Nuffield Council report on bioethics in developing nations, "in some societies it would be considered culturally inappropriate for researchers to ask individuals to participate in research without consulting the community or permission from community leaders." The report, which was updated in 2005, goes on to add that "in each of these circumstances, to seek consent from the individual without seeking consent from the leaders of the community or creating public acceptance of the research may be considered disrespectful and may harm relationships within that community."
The notion that a researcher could walk in with a six-page consent form and expect every research participant to understand and sign it "doesn't really make sense," Weale says. "You want to maintain high standards, but you want to do that in a culturally appropriate way."
Keeping research fair
There are even more problematic issues for de Vries, who has done most of her research on the African continent. "I think the more important issues have to do with justice and fairness and benefits for African populations," she says. "Genomics research in developing countries is still predominantly funded from the United States and various countries in Europe, most notably the UK. And that means that the research agendas are set by actors who are not in Africa, and the research methodologies are controlled by people who are not on this continent."
One "resounding" ethical dilemma for de Vries is the exportation of samples from the countries where they are collected to the US or Europe for analysis. While the objective is to do science that helps as many people as possible, with the continued extraction of genetic materials from Africa, the people of that continent have seen very little benefit in return, she adds. "The problem is that you want some of those benefits, at least, to flow to some of the people who are participating in the actual research. On the one hand, if genomics looks at a disease that is mostly prevalent [on this continent], then one argument could be that if you understand malaria better, or you find a cure, then it's only going to benefit people in developing countries," de Vries says. "But on the other hand, the question is: Who owns those drugs, who owns the patents, who owns the knowledge, who does the science? And very often it's not the African people."
Similarly, Oxford's Parker says, it's important that the sharing of data be done in a fair and equitable manner, not only to provide some benefit to the study participants, but also to protect the interests of local researchers. "How can you make sure that data sharing is done in a way that … doesn't undermine the capacity of local scientists to work on their own data?" he asks. "You release this data, and it gets used by the Wellcome Trust or the Sanger or the Broad. How can you make sure the scientists in developing countries get to work on their data?"
Though there are guidelines and standards for ethical research in developing countries, scientists are sometimes on their own, and are forced to come up with "practical solutions" that work in their given circumstances, Parker says. "Different cases in different settings are different, and you may need to think about community engagement or consent differently from East Africa to West Africa or in a rural area versus an urban area, et cetera," he says. "Guidelines can be competing or ambiguous or contradictory on the federal, local, and international levels. The guidelines don't always provide a straightforward answer to the question of 'How should I practice science in this setting?'"
Cape Town's de Vries has come up with a few practical solutions of her own in her years of experience, particularly when it comes to explaining her work to local populations. "I basically revert back to genetics," she says. "Explaining genomics is a bit too ambitious, and we can question whether it's fair that we explain genetics rather than genomics — it might not be. But I found that many people do have concepts of genetics that are integral to knowledge of who they are. The idea that you look like your grandfather or you have your grandmother's eyes, that basically talks about phenotypes to do with genetics. So if you revert back to that kind of knowledge, then that can be very useful."
Some solutions, however, will require more than improvisation by researchers, particularly when it comes to large-scale problems. For de Vries, sample exportation is an important issue, which she says will require institutional changes, both in the developed and developing world. One possible solution might be a model in which whenever samples leave Africa, for instance, a researcher from the country of origin hand-delivers them, visits the foreign labs where they are analyzed, and participates in the analysis, she says. "More genuine collaborative models, so that it's not just samples leaving and never coming back, but there is a genuine commitment to increase training as an integral part of the actual research — that is very important," de Vries adds.
What is also needed is political will in developing countries themselves to improve research and facilities, de Vries says. Many organizations in the US and Europe — the Bill and Melinda Gates Foundation, the National Institutes of Health, the Wellcome Trust — now include among their foci investigations of issues of health and science in the developing world with projects like MalariaGEN and the Human Heredity and Health in Africa Initiative. The governments of the countries where the research is conducted need to follow suit and commit to the establishmentand funding of research agendas and institutions, she adds.
Researchers also need resources they can rely on to give them advice and to help them work through any problems they may encounter. "My experience has been that the vast majority of scientists I've met are committed to doing the right thing and practicing science in an ethical way, and often they don't have the resources or the support to enable them to do that," Parker says. He suggests that researchers looking for advice start by examining the findings of groups like MalariaGEN, which have the resources they themselves might lack. In addition, "maybe they can build connections with local institutions. People often view ethics committees as some sort of hurdle that they have to go over, but my experience has often been that it's possible to have conversations with ethics committees that can lead to the development of these solutions," he adds.
Whatever the resolution, Parker says it's important for scientists to come up with answers that they can put to use in the field and can defend, if called upon to do so.
Research isn't going to stop until practical guidelines and solutions can be perfectly formulated, University College London's Weale says, so researchers have to do the best they can in the meantime. "I think the line the Nuffield Council would take is that there is an ethical imperative to conduct research to improve health," he says. "And while you need to ensure that that's conducted to high standards, there's a question about the judgment that's required as to what high standards mean in any given context." It would be unfortunate if research into important health and medical issues were halted because the researchers conducting the work couldn't guarantee the participants the same standard of care they would receive at an American or European institution, he says. "What we would say is: Don't make it a simple all-or-nothing affair, and think about what fair standards might be — high standards, aspirational standards," Weale says. "But you wouldn't say that what people can get in one part of the world they should be able to get in all parts of the world, because that would be unrealistic."