Mayo de 2016
Francisco Blancarte Jaber
An article published by Nature Biotechnology on 04/11/16, details a study conducted in which a screening of 874 genes in 589,306 genomes led to the identification of 13 adults with genetic mutations that should theoretically have led to the development of Mendelian conditions, and who nevertheless manifested no clinical indications of the diseases. These 13 individuals were labeled as ‘resilient’, in accordance with the name given to the study: ‘The Resilience Project’. Given the challenges that currently stymie the development of a biological cure for Mendelian diseases, the discovery of these 13 ‘resilient’ individuals, who would appear to possess some form of genetic and/or environmental modulation that suppress the effects of the disease-causing mutations, was a very promising outcome of the study.
Unfortunately, the scientists conducting this research study were unable to recontact any of the 13 ‘resilient’ individuals. This was due to the lack of the necessary clauses in the original informed consent forms used for the studies from which these individuals were identified. All the subjects in this study were gathered from already-existing genetic studies around the world. Through data access committees and collaboration with investigators corresponding to each particular database used by the study, the researchers were able to assemble and analyze the 589,306 individuals’ genetic data. Since the original consent forms for the genetic studies, from which all 13 ‘resilient’ individuals were identified, did not contain a clause permitting further contact by subsequent researchers, the scientists of this study were not legally permitted to contact the individuals in question.
The first regrettable consequence of this lack of recontact clause is that researchers were unable to perform additional critical preprocessing steps to further confirm the ‘resiliency’ of these 13 individuals. Such steps would have confirmed that the DNA matched the correct medical records for each individual, thus ensuring that this ‘resiliency’ was not a simple clerical error. This might be considered a redundancy, but given the potential benefit of further studying this ‘resiliency’, it would not have been wholly unnecessary to verify the results, especially given the relatively low ‘resiliency’ rate in this sample population (0.002%).
The reasons for recontact clauses are perfectly understandable. It is a necessary step, put in place to protect patients from being burdened by unwanted information. A patient might voluntarily participate in a research study wherein he or she provides a DNA sample and yet be entirely uninterested in finding out collaterally whether they possess a genetic mutation that could lead to a fatal and incurable disease.
One might reasonably argue that a patient could only benefit from having all possible information available to them. Information about a potential genetic disease might indeed be crucial, should a cure be readily available. Unfortunately, such is not the case for all genetic diseases, and it is thus perfectly understandable that a patient might not want to know that they suffer from an incurable disease.
Furthermore, there is the question of uncertainty regarding the results. However thorough the scientific method applied to the study of their DNA might be, a margin of error, however small and negligible, would still exist. This is without even mentioning the aspect of potentiality of developing the disease, accorded to the results. Indeed, even if the results are accurate, they often attribute a certain percentage of probability that the patient might develop the disease, meaning that even if the results were to indicate a 99% chance of developing the disease, there would still be a 1% chance that the patient won’t develop it. The argument against being informed of the results might then simply be the skepticism that a patient might hold against the results of the study.
The reality is that most results, and the consequent decisions that a patient has to make, are rarely simple. In most cases, though there may not be a cure for a genetic disease, there may very well be an array of possible treatments. The wide spectrum of possible outcomes, given the different forms of treatment available for a disease, make the decision of wanting to be informed of potential genetic diseases even more complex. Additionally, it would not be unreasonable to assume that some patients involved in this study would surely want to be informed that they possess a genetic advantage that renders them immune to a certain disease. Furthermore, an altruistic inclination might very well persuade them to agree to further testing, if they thought it could potentially lead to a cure that would help people suffering from the disease.
The prospect of establishing a comprehensive legal framework to the aspect of recontact clauses in informed consent forms for research studies, one that would take into account all the aforementioned complexities and could thus ensure that the patient’s wishes were respected given every possible scenario, is daunting to say the least. Nevertheless, the potential benefits of such amendments, as evidenced by this particular case, make it imperative that we address that challenge.