Advances in technology have made it possible to sequence a whole human genome [1,2]. National and international funding initiatives have stimulated whole-genome research activities [3,4], and media coverage of both the science [5,6] and the emerging commercial offerings [7,8] related to genome research has heightened public awareness and interest in personal genomics. As technology continues to advance, whole-genome research activities seem likely to intensify and expand, necessitating carefully considered consensus guidelines for ethical research practice.
To date, there has been only minimal consideration of the research ethics issues associated with this work [9–12]. We therefore convened an interdisciplinary consensus workshop to develop ethically rigorous and practical guidance for investigators and research ethics boards. What follows are recommendations on the four topics that were the focus of the workshop. These topics—consent, withdrawal from research, return of research results, and public data release—were selected because they were viewed as being among the most pressing research ethics issues and as representing areas where whole-genome analysis creates unique challenges. They are not, of course, the only policy issues that need to be considered; commercialization, patenting, benefit sharing, and the possibility of genetic discrimination are among other topics that warrant reflection. Regardless, the four topics covered in this paper are current issues worthy of immediate attention.
The paper starts with initial considerations, including general recommendations about governance and the characterization of the research activities related to the whole genome. It is important to note that while there was consensus on all recommendations, there was a good deal of debate about the degree to which they satisfy existing ethical and legal norms . All participants believed that we need both empirical research and continued conceptual analysis (Box 1). These are early days in the field of whole-genome research. Research ethics guidance is needed immediately, but we should continue to explore the ethical, legal, and social implications of this rapidly evolving field (Box 2). Indeed, the door must remain open for further reflection on these and other social concerns.
Box 1. Ethical Questions for the Future
The following is a list of research ethics questions that warrant future investigation and analysis. It is not an exhaustive list of the research ethics questions associated with whole-genome research.
- Duty to Recontact: Given the numerous disciplines and health care providers potentially involved in whole-genome research, further analysis of the legal and ethical obligations of each (particularly in the context of return of results) seems warranted. Who has what obligations? Who, if anyone, has the duty to return results? Is there a “chain of obligation” that runs through the various members of a research team?
- Right to Withdraw: Because of the potential for the rapid dissemination of research results, the right to withdraw can quickly become impractical. This raises the issue of the degree to which there is an ethical requirement to structure the research and dissemination of results in a manner that will allow the right to withdraw to endure as long as possible. As such, this issue should be investigated with consideration of existing and evolving legal and ethical norms, emerging information technology tools that may facilitate withdrawal, and governance structures that can be implemented.
- Risk/Benefit Analysis: There is a need for a comprehensive risk/benefit analysis of public data sharing. Studies that explore the impact on research of restricted access versus open access would be useful, and should include a consideration of costs and actual risk of harm.
- Governance Structures: There is a need to systematically evaluate existing and emerging governance structures. This should include a consideration of the ways in which new information technologies can be utilized to facilitate, inter alia: continued communication with participants; the continued right to withdraw; and, when appropriate, community engagement.
Box 2. Personal Genome Research: What Are the Possible Risks?
By Timothy Caulfield, Mildred Cho, and Amy McGuire
The ability to sequence an individual's entire genome will allow for the production of an unprecedented amount of detailed genetic information, helping researchers to explore the relationship of genes and environment in the development of a wide variety of human diseases.
But imagine being a research participant in this exciting new field. Researchers would be seeking to produce a record of all your genetic information. As a result, all known genetic predispositions will be available and, depending on the data sharing policy, accessible to a wide range of researchers and, possibly, the public at large—this, at a time when we are still seeking to understand the social, clinical, and personal implications of genetic information.
These uncertainties can create unique ethical challenges. What do you tell potential participants during the consent process about risks when we still don't have a clear sense of their nature? Also, it is difficult to know, at the time of recruitment, exactly how the genetic information will be used, and by whom.
While most of the risks remain speculative, and we imagine that much of this research will be conducted by highly respected researchers at leading academic centers, one can imagine a number of controversial scenarios. Some of these may seem far-fetched, and we do not intend to be alarmist, but it is important to recognize that just one breach similar to those described below, or even the threat of such a breach, could hurt public trust and significantly hamper the ability to conduct genetic research.
Imagine you are watching the news and learn about a study linking race to IQ, which you find offensive. You later learn that they used your DNA for this study. You donated your DNA five years ago for use in a genetic association study of cancer and heart disease. At the time, you were told that other researchers might want to use your DNA for other types of research. You want to withdraw your consent, but it is too late. Your genetic information has been analyzed by many researchers and is now integrated in databanks throughout the world.
Imagine that you are sitting home, minding your own business, and the police show up at your door with a search warrant. They are looking for the suspect from a crime scene 2,000 miles away in Des Moines, Iowa. It turns out that some DNA that was left at the crime scene matched a sample from a publicly accessible scientific database that contained DNA from one of your brothers.
Imagine that at the time you first donated your sample for genetic research, it was explained as part of the consent process that no information about your genetics would be returned to you. Years later, you develop a heritable form of cancer and learn that the research team must have known you were genetically predisposed to the disease. To complicate matters further, you have a large number of siblings, none of whom want to know about their genetic predispositions. This information is now available to all.
Imagine you just opened your own electronics recycling business and are trying to find private health insurance. Your friend recommends that you contact a specific company. As part of the enrollment process, the company finds out that you participated in a genetic study and that your genetic information has been released into a publicly accessible database. By accessing the database, the company finds out that you are at increased risk of early-onset Alzheimer disease and are highly susceptible to cancer from the chemicals encountered in your recycling process. They also find that you are at greatly increased risk of colon cancer, which alerts you to now take early screening and preventive measures.
This is, no doubt, an exciting time for genetic research. And it cannot move forward without research participants. As such, it is important to note that the risks associated with this kind of research may be limited and controversial events rare. But history has told us that they do occur and can have a devastating impact on public trust and the research environment. It is therefore critical that as this research moves forward, there are guidelines in place, such as those outlined by this paper, to promote ethical research conduct and to help avoid, as much as possible, scenarios like those described above.