Editorial: With great power comes great responsibility for NCGENES project

UNC researchers are currently leading the genomic revolution by implementing Whole Exome Sequencing in the clinic. 

In 1990, the National Institutes of Health (NIH) embarked on the Human Genome project, a 13-year-long, publicly-funded effort with the end goal of identifying the DNA sequence of the entire human genome. Sequencing the first genome cost about $1 billion, but today it costs about $3,000 to $5,000 and takes only one to two days. However, there are many subsets of next-generation sequencing that are proven to be effective as well, such as whole exome sequencing. 

This type of sequencing is a genetic test that only sequences the DNA in your body that code for proteins, which join together to give you genes that produce eye color, height and even potential diseases that you may have. Scientists have been using this tool in research for nearly two decades, but recently, the age-old question has arisen: Can sequencing be used in routine medical care?

This is exactly what researchers, geneticists, doctors and bioethicists at UNC want to find out. NCGENES was born out of a four-year, $6.4 million NIH-funded grant that was used to sequence genomes of hundreds of patients to develop diagnostic markers for clinicians. In 2017, the NIH renewed the grant for $9.7 million, to establish what is known to most UNC professors as NCGENES 2, led by Dr. Jonathan Berg. 

The entire project has three known “waves”: Clinical Genomic Study, in which the use of whole exome sequencing in the clinic is evaluated; Analysis and Interpretation of Sequencing Data, and Ethical and Psychosocial Implications Research. Researchers hope that by completing this project, UNC will be able to develop an infrastructure to apply genomic sequencing for the benefit of patients within the clinic. Eventually, they hope to apply these sequencing techniques in order to serve medically-underserved groups and populations.

Regardless of how fast and cheap genetic sequencing may have grown over the last two decades, the feat of accurately and effectively interpreting genomic results is not to be taken lightly, and poses numerous ethical considerations.

The first being, genomics is a probabilistic science; even though one may have a certain DNA sequence, there are a variety of other things that can affect which genes are actually expressed. Environmental, biological or geographical factors, and not to mention genetic variation and mutation, can all play a role. In addition, it is not just one gene or sequence that can be used to identify certain traits — most of the time, multiple genes code for one trait. This makes it exponentially more difficult for researchers to be able to definitively draw conclusions based on sequencing results.

However, what researchers can draw upon more reliably from sequencing results are genetic risks. As a more popular example, genetic counselors have been able to identify from extensive testing that individuals with a mutation in the BRCA1 or BRCA2 gene have around a 40 percent higher chance of acquiring breast cancer in their lifetimes. 

Because of the inability of researchers to pinpoint exact risks of certain genetic diseases, obtaining information about one’s genetic risk for a disorder can have severe impacts on quality of life and cause significant stress. This can lead to potential stereotyping and stigmatization from members of other populations. 

Psychological research has identified that individuals who learn of their risk for potentially life-threatening illnesses, such as mutation in the BRCA gene, are at extremely high risk for negative medical outcomes, and are likely to be in need of psychological services.

It’s no secret that genetic testing is moving faster than legislature can keep up. In the world of research, it is expected for scientists to publish data for further analysis by the scientific community. Although genetic data released into databases are not linked to your name, your DNA sequence is your own, and can be easily identifiable given that medical-sequencing data can also include demographic, clinical, exposure and employment information, as well as family pedigrees. 

Apart from the Genetic Information Nondiscrimination Act passed in 2008, which protects against discrimination from employers and health insurance, there is no legislation on how genetic data can be used by life insurance companies or educational institutions.  This can potentially be dangerous for individuals who get tested for expensive conditions that may be denied coverage or protection under the law. 

In addition, before research projects are undertaken, patients must be able to give consent with the knowledge of how their data will be used in the future, but because of the speed of the new technologies being developed, it is difficult for researchers to be aware of the scope of future applications of that data, bringing into question the viability of consent provided by the patient.

The NCGENES project has and currently employs bioethicists to aid in study design and execution. They are included with the hope of addressing these lofty, ethical questions that may affect patients enrolled in the study. However, the study design has left ethical and psychosocial implications research to be addressed in the final project, which will likely not be studied until after NCGENES 2 has been completed. 

Although this project puts UNC at the forefront of the genomic revolution and research, it is incredibly important to have the patients' best interest in mind and to continue considering the bioethical implications of the cutting-edge work being done here in Chapel Hill.