WORCESTER MEDICINE
Game Changers
Descciated Scabs to Genomic Vaccines Continued clearance the following week. The platforms for synthesizing mRNA vaccines created an enormous number of doses. By the end of August 2021, approximately 350 million doses of the two mRNA vaccines had been administered to residents of the United States. Epidemiologists have estimated the two vaccines, which had demonstrated efficacies of greater than 90% in persons of all ages in reducing the risk of hospitalization and death, have saved tens of thousands of hospitalizations and lives. The stunning introduction and efficacy of the mRNA vaccines have not been without controversy due to misinformation, especially regarding a belief that the vaccine can alter a recipient’s DNA. In fact, the mRNA injected into the muscle cells of the upper arm promptly instructs the cells to produce the RBD of the spike protein, but it does not enter the cell’s nucleus or comingle with the host’s DNA. Indeed, being a fragile molecule, the mRNA disintegrates about 72 hours after entering muscle cells. The spike RBD protein produced in response to the mRNA is seen as foreign and as such elicits a cellular and humoral immune response, the latter including the production of neutralizing antibodies. These antibodies bind to the spike’s RBD, which is responsible for attaching to host-cell receptors; the angiotensin converting enzyme, or ACE2; and initiating host-cell invasion. Thus, neutralized by antibodies, SARS-CoV-2 cannot infect targeted cells and the recipient’s DNA remains intact and unaltered. Given the impact of global warming, the extent of human intrusion on ecosystems and the scope of international travel, the likelihood of another coronavirus or other viral pandemic appears almost certain. One reassuring lesson from the current crisis is that the scientific ability to swiftly characterize novel microbes to the atomic level is remarkable and without precedent. Similarly, the ability of dedicated researchers to elucidate interactions between microbe and host at the molecular level is equally breathtaking. Finally, the ability of governments and private industry to work together to produce and distribute life-saving vaccines is equally impressive. In short, medical science has come a long way from using desiccated scabs to inoculate susceptible populations. However, it is worth remembering, “antivaxxers” agitating in 2021 were preceded by those in the 1800s who found the smallpox vaccine unacceptable and who resisted its introduction. So, while mRNA vaccines should be considered game changers in medicine, human nature appears sadly unyielding in its adherence to irrational, narcissistic and self-destructive impulses. + Anthony L. Esposito, MD Hospital Epidemiologist, Saint Vincent Hospital Professor of Medicine University of Massachusetts School of Medicine George Abraham, MD Chief of Medicine, Saint Vincent Hospital Professor of Medicine University of Massachusetts School of Medicine
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Amplify Your Practice With Point of Care Polymerase Chain Reaction (PCR) Testing Craig M. Lilly, MD Nathaniel Hafer, PhD
E
xtraordinary advances in the ability to
rapidly and accurately determine the coding sequences of DNA have taken place in the past 25 years. A xerox-like technology called the polymerase chain reaction, or PCR, was developed that allowed minute samples to be amplified to an amount sufficient for sequencing (decoding). This advance won its inventor, Cary Mullis, the 1993 Nobel Prize in chemistry. Subsequently, the methods for determining the sequence of code letters of DNA and RNA in clinical samples has reached a new level of convenience. PCR technologies have led to an increasing number of clinical applications and have recently been at the forefront of public health recommendations during the COVID-19 pandemic. Here, we will briefly describe how PCR works, and its potential pitfalls, followed by a description of tests available for clinicians to diagnose and manage diseases. We will also discuss the availability of these tests in a point of care format that can provide immediate access to test results at a patisent’s home or in their physician’s office. PCR tests detect nucleic acid sequences by cyclical amplification. The specificity of the reaction is determined by a pair of “primers” that bind to sites on opposite ends of a DNA or RNA molecule. Enzymatic addition of complementary nucleotides to those of the target sequence fill in the space between the primers and generate a complementary strand comprised of nucleotides that correspond to those of the original target — i.e. guanine corresponds to cytosine. The target and complementary strands are then separated by heating the reaction mixture and the primers and then attaching both to the original target and the newly synthesized copies to generate an exponential number of copies during subsequent amplification cycles. A key feature of the method is that the copying enzyme, called a DNA polymerase, is a special in that it can withstand the repeated heating steps. It was discovered in a primitive organism that
NOVEMBER / DECEMBER 2021
