In 1977, English biochemist, Fredrick Sanger, created the first full genome sequencing technique, mapping the complete arrangement of genes in a given genome. His method involved electrophoresis and chain-termination. DNA is made up of smaller units called nucleotides. Sanger used modified nucleotides called dideoxynucleotides (ddNTP), which bond to only a single end of nucleotides, breaking long strands of DNA into smaller pieces. He would run four separate reactions, each containing one of the a different types of ddNTP that would bond, and, in turn, cut the DNA at a specific spot. Then, he separated the products of these reactions by size on a special type of gel called polyacrylamide gel, which divides the reactions into four lanes. When the products are placed on this gel, they form bands that are visible through a technique called autoradiography. The bands would show the sequence of nucleotides in the original DNA sample, and, by examining the position of each band in each lane, the order of the nucleotides in the DNA sequence could be determined. Such genetic sequencing, dubbed first-generation or “Sanger sequencing,” was used in the Human Genome Project, an international effort to map the entire human genome. The thirteenth-year long project was finalized in 2003 and, since its completion, genomic sequencing has proven itself critical to modern healthcare.
Advancements in first-generation sequencing and the creation of second-generation and next-generation sequencing (NGS) have made whole-genome sequencing significantly cheaper, faster, and more precise than its early stages in the Human Genome Project. One significant improvement to first-generation sequencing was use of fluorometric-based detection instead of radiolabelling technique. In flouronetric-bsed detection, dyes are used to label the nucleotides that are incorporated into a growing DNA strand during the sequencing reaction. By measuring the fluorescence emitted by each nucleotide, the identity of the nucleotide can be determined and, thus, the sequence of the DNA. This allows the sequencing reaction to take place in a single container instead of four, simplifying the process. Another improvement was the use of capillary-based electrophoresis, which allowed for more accurate and faster detection of the DNA fragments produced in the sequencing reaction. Capillary-based electrophoresis involves placing the DNA fragments in a capillary tube filled with a gel-like substance and applying an electric field to cause the fragments to move through the gel. As the fragments move through the capillary, they are separated by size and detected by a detector at the end of the capillary. These enhancements, in combination with other technical developments, led to the creation of automated DNA sequencing machines, which could sequence genomes more quickly and efficiently than previous methods. The first commercial DNA sequencing machines were created using these improvements and were used to sequence the genomes of increasingly complex organisms.
NGS, on the otherhand, is characterized by its mass parallelisation of sequencing reactions. Essentially, while Sanger sequencing can only sequence one DNA fragment at a time, NGS can sequence millions of fragments simultaneously. With NGS, it is possible to sequence an entire human genome in a single day, which greatly reduces the cost involved in DNA sequencing.
Today genetic testing is ubiquitous. People seek genetic consultations from health care centers, using blood, hair, skin, or other sampels to collect DNA. Genomic sequencing is then performed in a laboratory, in which scientists analyze results, consult with genetic counselors, and share data with patients. It can be particularly effective in diagnosing rare diseases that would otherwise require extensive, specific testing, including Huntington’s disease and some forms of ALS. Undercutting such breakthroughs in medical genetics, however, is serious concern over consumer privacy. Many genetic testing results are uploaded to large data platforms. Such information enables scientists to track outbreak patterns and better understand unique diseases, but broad data sets can also threaten the privacy of individuals. According to the Journal of Law and the Biosciences, “Millions of people are compelled every year to provide unlimited access to their health information for various uses, such as insurance and commercial transactions.” As more third-party entities are gaining access to this sensitive data, hackers can make fake patient profiles, file fraudulent insurance claims, and track patients’ relatives.
To address genomic security, the United States federal government has enacted several policies. In 1981, the Common Rule was passed, requiring patients to provide informed consent about the limitations and consequences of sequencing. And in 2008, the Genetic Information Nondiscrimination Act (GINA) was established to prevent genetic discrimination, restricting employers and health insurance issuers from viewing genetic data. Furthermore, the Health Insurance Portability and Accountability Act Privacy Rule uphold’s patients’ anonymity. Other policies include Certificates of Confidentiality and the Freedom of Information Act (FOIA).
Despite these governmental efforts to enhance genomic security, privacy remains a pressing issue in genetic testing. The HIPAA Privacy Rule, for example, contains dangerous exceptions for user data protection. When patients sign genetic testing privacy forms, they believe their security is prioritized. However, HIPAA has many gaps that allow several entities to access individual and identifiable data. Specifically, there are twelve exceptions, known as “public purpose” exceptions, that allow healthcare entities to share protected health information, including genetic information, without an individual’s authorization or consent. These exceptions include situations where protected health information is required by law, for public health activities, for victims of abuse or domestic violence, for health oversight activities, for judicial and administrative proceedings, for law enforcement, for decedents, for organ or tissue donation, for certain types of research, to avert a serious threat to health or safety, for specialized government functions, including national security, and for workers’ compensation. The Privacy Rule doesn’t mandate any disclosures under these exceptions. Any requirement for healthcare entities to share information, such as to notify public health agencies about certain infectious diseases, are governed by separate federal or state laws. As genetic testing expands, millions of people are contributing their data to broad platforms, where others could potentially access their information without explicit consent.
Scientific innovations are increasing more rapidly than ever before, genomic sequencing among them. A publication from the Tony Blair Institute for Global Change states, “There are few technologies that promise to be as informative and transformative as genomics. From the improvements to personalised medicine and national and international public health policy to the economic gains generated by improved health and crop management, governments will be hard-pressed to find a better value for money proposition. Investment in national and regional genomics facilities should be a first order priority in advancing the future of health.” While genomic sequencing is critical to our future, privacy is just as important. Each patient’s medical data must be protected. Tightening policies and improving database security are essential components of ethical genetics. Additionally, increased privacy makes more patients comfortable with participating in sequencing and, thus, further scientific research, benefiting everyone. By raising awareness about privacy issues, enhancing laws, and strengthening information security, we can reap the benefits of safe and ethical genomic sequencing.
