The work of geneticists, a category that includes the majority of Genomes Unzipped contributors, typically consists of analyzing DNA sequences from large collection of individuals and this constant flow of data gives us an overview of the diversity of human genotypes. And while in most cases these mutations do not have any functional impact, some rare cases are well documented and have important adverse effects.
A famous example is the BRCA2 gene for which rare mutations have been linked to an increase prevalence of breast and ovarian cancer. Another example: multiple rare variants have been linked to various forms of familial hypercholesterolemia, a condition that significantly increases heart disease risk. I picked these examples because for both cases the identification of carriers of these rare mutations in the general population could improve health: aggressive detection of breast cancer, and use of relevant treatments (such as statins) if you are a familial hypercholesterolemia patient, can make a real difference.
The fact that, in some cases at least, something can be done can put geneticists in a difficult situation. Indeed, we often come across known disease related mutations in the DNA from patients who were not recruited for anything linked to that disease. And it is not clear how this information should be handled. On one hand, we cannot assume that the patient has any desire of knowing anything about his/her disease risk. On the other hand, while analysts always work on anonymous genetic data, the medical staff that collected the sample could potentially get back in touch with the patient who donated his/her DNA. Letting DNA donors know may actually make a difference in their lives (again, this situation is rare but it happens).
What is the legal situation?
Rather systematically research consent forms for DNA donations are overly cautious and do not provide any opportunity to get back to the donor. The current view is that tissue donation, including DNA samples, are considered as gift from the the donor to the researcher (see for example this document from the MRC). And often it is even not practically possible to get back to the patients because the samples have been anonymized (see the Wellcome Trust Case Control Consortium FAQ for example).
There are plenty of be good reasons to not feedback these data, the most important being the practical means by which the patient can be contacted and what he/she should be told whatever information is relevant. In many cases, while we have strong suspicions on the role of some mutations, we are not absolutely sure either. Overall, I find this inability to share useful information with patients potentially eager to obtain this information a frustrating part of my work.
How could we provide this information in a useful way?
This uncertainty is a major hurdle: no one wants to cause panic by suggesting a high cancer risk to a patient who has no reason to worry. Researchers work with doubt and questioning all the time, but most individuals just want a clear assessment of risk and are not at all interested in a lengthy research discussion. And researchers are not at all trained to communicate with patients.
Daniel MacArthur and others have previously suggested (see this and this) an alternative approach that seems rather appealing: this expertise in communicating genetic results to non-scientists is the main strength of direct to consumer (DTC) genetic companies like 23andMe or deCODEme. Their webpages are clear, simple to follow, and they do provide reasonably accurate information. They also know how to deal with legal and technical issues associated with communicating genetic data.
So here is a potential scenario that would address these issues: researchers collecting DNA provide each donor with a barcode associated with their samples. Once generated, data and the barcode are then sent to a DTC private genetic company that will not process the data until the donor decides to claim his/her barcode. Once this happens, the company processes the data and shares with the donor whatever the DTC company thinks is worth knowing. This process would build a partnership between the research institution and the DTC company. It would probably take the data generation step off the hands of the DTC company, but would take advantage of its expertise in communicating the results of the study to interested donors. It would be beneficial to the individuals involved in the study, who would then have a choice to know or ignore the results. It would probably also motivate more individuals to contribute to genetic studies, something of interest to researchers because we need donors of course.
A last addition to this setup would be the opportunity for individuals to make their DNA data available on demand for future studies. For example, because I am in general very willing to be involved in genetic research studies I gave blood and consented to be genotyped several times already, including once I paid for when I used 23andMe services. Of course this redundancy is largely a waste of money. Therefore, a UK research council (taxpayer’s money!) will pay a few hundreds of dollars for a work which has, for the most part, already been paid for by myself willingly. If I could have just shared these data with the researchers taking my blood, it would have been much more efficient.
This approach leads to the idea of a patient being actively involved in multiple research studies at low cost, and something very much within the scope of what 23andMe wants to achieve. Indeed, a recent recent 23andMe publication illustrates the power of this approach. Luke Jostins, another Genomes Unzipped blogger, has commented on this idea already (and so has Daniel McArthur in this post).
Technical arguments against this idea
An important concern is the ability of this suggested pipeline to feedback genetic data. Existing diagnostic labs go through formal rounds of accreditation to guarantee high quality analysis. For example genetic researchers often deal with processing errors and sample swaps (at least I do), and it is likely that in some cases the data will be sent to the wrong individuals. See for example the recent disaster generated by a sample swap in the 23andMe pipeline. Of course these issues affect any lab and I am not sure that 23andMe is in any way more likely to mess it up than the safest accredited government laboratory.
Moreover, if the findings have important consequences for the donor, repeating the analysis is essential to verify what was found. This will not always be possible in a research setting. If mistakes (like sample swaps) are too common, the resulting cost benefit of sharing these data with the donors will be poor. Consequently, it is likely that each research study will be judged based on its ability to ensure proper sample handling as well as the ability to recontact DNA donors if required. We should therefore expect the rules to vary across research studies.
And ethical arguments against this idea
In addition to these technical issues there are deeper ethical concerns. As mentioned above, the current view is that tissue donations, including DNA samples, are considered as gifts from the donor to the researcher. Within this framework there is no reason for the donor to retain ownership of the data generated. Providing potentially expensive information back to the patient would change the balance between donor and researcher. For example, if donors get involved in the study in order to get their DNA sequenced, they may decide that subsequent studies are not worth the effort once they have obtained the genetic data they were looking for. This type of commercial relationship is certainly not what researchers want to build with individuals donating DNA samples.
In my view, providing the DNA data back to donors is a goal we should be aiming at. The “gift” idea is only the best framework researchers have found so far, but moving away from this is plausible and is unlikely to radically affect the donor-researcher relationship. It is however hard to be certain. Moreover, we do not yet know what the impact of general feedback of DNA data to donors will implicate and given the potential for harm we should be careful. A stepwise process, using DTC companies or not, but starting with small subsets of patients, should be conducted as soon as possible to evaluate the consequences of these changes. It would certainly be disappointing if the overly cautious approach of doing nothing prevailed.